Method of identifying agents that modulate UCP2 promoter activity

The invention relates to regulators of UCP2 gene transcription, including novel UCP2 transcriptional promoters. UCP2 gene promoters are used in diagnosis and pharmaceutical development. In particular, transfected cells comprising UCP2 gene promoters operably linked to a reporter are used in high-throughput pharmaceutical screens.

Human telomerase RNA interacting protein gene

The invention provides methods and compositions relating to a human telomerase and related nucleic acids, including four distinct human telomerase subunit proteins called p140, p105, p48 and p43 having human telomerae-specific activity. The proteins may be produced recombinantly from transformed host cells from the disclosed telomerase encoding nucleic acids or purified from human cells. Also included are human telomerase RNA components, as well as specific, functional derivative thereof. The invention provides isolated telomerase hybridization probes and primers capable of specifically hybridizing with the disclosed telomerase gene, telomerase-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

CXCR3 antagonists

Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.

Monitoring of gene expression by detecting hybridization to nucleic acid arrays using anti-heteronucleic acid antibodies

The present invention relates to anti-heteronucleic acid antibodies and their uses for detection of RNA-DNA duplexes on arrays. The invention provides a method for detection of total cellular RNA hybridization on microarrays, thus obviating the need for isolation of the poly(A)+ fraction.

Fused bicyclic nitrogen-containing heterocycles

Compounds, pharmaceutical compositions and methods that are useful in the treatment or prevention of metabolic and cell proliferative diseases or conditions are provided herein. In particular, the invention provides compounds which modulate the activity of proteins involved in lipid metabolism and cell proliferation.

IKAP proteins and methods

The invention provides methods and compositions relating to IKAP proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKAP encoding nucleic acids or purified from human cells. The invention provides isolated IKAP hybridization probes and primers capable of specifically hybridizing with the disclosed IKAP genes, IKAP-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Arylsulfonanilide derivatives

The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Screening method for agents that modulate human NIK activity

The invention provides methods and compositions relating to a novel kinase, NIK, involved in NFκB activation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed NIK encoding nucleic acids or purified from human cells. The invention provides isolated NIK hybridization probes and primers capable of specifically hybridizing with the disclosed NIK genes, NIK-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Pyrimidine derivatives

Compounds and compositions are provided which are useful for the treatment of viral infections, particularly human Cytomegalovirus infection. The compounds include novel pyrimidine-based derivatives.

High-throughput in vitro assays for modulators of peptidyl transferase

High-throughput in vitro assays are provided for identifying modulators of peptidyl transferase. New solid-phase assays, related compositions, apparatus and integrated systems are provided.

Inflammation modulators

Compounds, compositions and methods that are useful in the treatment of inflammatory, immunoregulatory, metabolic and cell proliferative conditions or diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, metabolism and cell proliferation. The subject compounds contain quinoline or quinazoline rings.

CYP7 promoter-binding factors

The invention provides methods and compositions relating to CPF proteins which regulate transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed CPF encoding nucleic acids or purified from human cells. The invention provides isolated CPF hybridization probes and primers capable of specifically hybridizing with the disclosed CPF genes, CPF-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

High-throughput screening assays for modulators of nucleic acid topoisomerases

This invention provides novel assays for topoisomerase activity and for identifying topoisomerase inhibitors. The assays include both solid-phase and liquid-phase methods that are amenable to high throughput screening methods. The assays of the invention are readily adaptable to numerous types of topoisomerase, and are capable of identifying novel classes of topoisomerase activity modulators.

LXR modulators

The invention provides compounds, compositions and methods for modulating the effects of LXR in a cell. The compounds and compositions are useful both as diagnostic indicators of LXR function and as pharmacologically active agents. The compounds and compositions find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.

G-protein coupled receptor BCA-GPCR-3

The invention provides isolated nucleic acid and amino acid sequences of four novel G-protein coupled receptors that are amplified in breast cancer cells, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of G-protein coupled receptors.

Combination therapeutic compositions and method of use

The present invention provides pharmaceutical compositions and methods for the treatment of diabetes mellitus using combination therapy. The compositions relate to a compound of Formula I and an antidiabetic agent such as sulfonylureas, biguanides, glitazones, α-glucosidase inhibitors, potassium channel antagonists, aldose reductase inhibitors, glucagon antagonists, activators of RXR, insulin therapy or other anti-obesity agent. The methods include the administration of the combination of compound of Formula I with antidiabetic agent where the two components are delivered in a simultaneous manner, where the compound of Formula I is administered first, followed by the antidiabetic agent, as well as wherein the antidiabetic agent is delivered first followed by the compound of Formula I.

Pentafluorobenzenesulfonamides and analogs

The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, vascular restenosis, microbial infections, and psoriasis, or as lead compounds for the development of such agents. The compositions include compounds of the general formula I:

Nuclear factors and binding assays

The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by a transcription complex containing at least a human nuclear factor of activated T-cells (hNFAT). The materials include a family of hNFAT proteins, active fragments thereof, and nucleic acids encoding them. The methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Cell-based drug screens for regulators of gene expression

The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Methods of using pyrimidine-based antiviral agents

The invention provides novel methods of using substituted pyrimidine compounds and compositions for the treatment or prevention of diseases associated with CMV infection. In particular, the present invention provides methods for the treatment or prevention of cardiovascular diseases and organ transplant rejection.

FXR modulators

The present invention provides compounds, pharmaceutical compositions and methods that are useful in modulating the farnesoid X receptor (FXR). As FXR is involved in negatively controlling the expression level of cholesterol 7α-hydroxylase (cyp7a), the rate-limiting enzyme involved in the oxidative metabolism of cholesterol into bile acids, the compounds described herein find utility in treating diseases associated with abnormally high or low cholesterol levels. In certain aspects, the FXR modulators (e.g., antagonists) described herein block the negative feed-back downregulation of cyp7a expression produced by certain cholic acids, the endogenous ligands for FXR. Moreover, as FXR forms heterodimers with the retinoid X receptor (RXR) in some cell types, modulation of the level of FXR activity in cells has a wide range of effects on a variety of biological processes which are mediated by RXR or other RXR-interacting proteins such as PPARγ and PPARα. Thus, compounds described herein are useful ...

IRAK-4: COMPOSITIONS AND METHODS OF USE

Arylsulfonamidobenzylic compounds

Arylsulfonamidobenzyl alcohols, amines and sulfonamides are provided which are useful in treating lipid disorders, metabolic diseases and cell-proliferative diseases.

Nuclear hormone receptor fluorescence polarization assay

Methods for identifying modulators of nuclear hormone receptor function comprise the steps of (a) forming a mixture comprising a nuclear hormone receptor, a peptide sensor and a candidate agent, but not a natural coactivator protein of the receptor, wherein the sensor provides direct, in vitro binding to the receptor under assay conditions; (b) measuring an agent-biased binding of the sensor to the receptor; and (c) comparing the agent-biased binding with a corresponding unbiased binding of the sensor to the receptor. In particular embodiments, the sensor comprises an amphipathic alpha helix nuclear hormone interacting domain comprising a recited nuclear hormone transcriptional coactivator motif sequence, the sensor is present at sub-micromolar concentration, the binding reaction occurs in solution, the sensor comprises a fluorescent label and the measuring step comprises detecting fluorescence polarization of the label. Reagents include labeled sensor peptides and reaction mixtures consisting ...

Combination therapy using pentafluorobenzenesulfonamides

Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic platinum coordination complex such as cisplatin.

IκB kinases

The invention provides methods and compositions relating to IκB regulating proteins, known as T2K proteins, and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed T2K encoding nucleic acid or purified from human cells. The invention provides specific hybridization probes and primers capable of specifically hybridizing with the disclosed T2K gene, T2K-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Chandra: a TH1-specific gene

The present invention provides nucleic acid and protein sequences for a Th-1 cell-specific protein, Chandra. The herein-disclosed sequences can be used for any of a number of purposes, including for the specific detection of Th1 lymphocytes, for the identification of molecules that associate with and/or modulate the activity of Chandra, to diagnose any of a number of conditions associated with Th1 or Th2 cell activity, or to modulate the number and/or activity of Th1 or Th2 lymphocytes in a mammal.

Arylsulfonamidobenzylic compounds

Arylsulfonamidobenzyl alcohols, amines and sulfonamides are provided which are useful in treating lipid disorders, metabolic diseases and cell-proliferative diseases.

Antiinflammation agents

Compounds, compositions and methods that are useful in the treatment of inflammatory, immunoregulatory, metabolic, infectious and cell proliferative diseases or conditions are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, metabolism, infection and cell proliferation. The subject compounds contain a fused heterobicyclic ring.

Modulation of CCR4 function

Compounds and compositions are provided that bind to the CCR4 chemokine receptor and which are useful for treating diseases associated with CCR4 activity, such as contact hypersensitivity.

TRAF2-associated protein kinase and assays

The invention provides methods and compositions relating to a novel human tumor necrosis factor receptor associated factor number two associated kinase protein. The invention provides hybridization probes and primers capable of hybridizing with the disclosed gene, nucleic acids encoding the kinase, methods of making the kinase proteins, and methods of using the compositions in diagnosis and drug screening.

Certain polycyclic compounds useful as tubulin-binding agents

Derivatives of known tubulin-binding compounds are provided in which a (poly)fluorobenzene, a fluoropyridine, or a fluoronitrobenzene moiety is incorporated or added to the structure. These derivatives can be used as antimitotic agents and can be considered covalent modifiers of tubulin. The strategy developed for each of the compounds is to i) append a fluorinated electrophile (e.g., pentafluorophenylsulfonamido, 2-fluoropyridyl, or 3,5-dinitro-4-fluorophenyl) to an existing functional group in a natural product, ii) replace an aromatic ring in a natural product with a fluorinated electrophile, or iii) attach a fluorinated electrophile to an open valence in a portion of the molecule that will not interfere with recognition and binding to the tubulin site. Derivatives are provided based on colchicine, steganacin, podophyllotoxin, nocodazole, combretastatin, curacin A, vinblastine, vincristine, dolastatin, 2-methoxyestradiol, dihydroxy-pentamethoxyflavanone and others.

Modulation of CCR4 function

Compounds and compositions are provided that bind to the CCR4 chemokine receptor and which are useful for treating diseases associated with CCR4 activity, such as contact hypersensitivity.

IKK-ALPHA PROTEINS, NUCLEIC ACIDS AND METHODS

NS5B HCV polymerase inhibitors

Compounds, compositions and methods are provided that are useful in the treatment and prevention of certain viral infections and associated diseases. In particular, the compounds of the invention inhibit the activity of a viral RNA polymerase. The subject methods are particularly useful in the treatment of diseases causes by hepatitis C virus infection.

IRAK-4: compositions and methods of use

The present invention provides nucleic acids and polypeptides for IRAK-4, a novel member of the IRAK family of protein kinases. Members of the IRAK family are indispensable signal transducer for members of the IL-1R/Toll family of transmembrane receptors, including IL-1 receptors, IL-18 receptors and LPS receptors. IRAK-4 sequences from human and mouse are provided, as are methods for identifying compounds useful in the treatment or prevention of inflammatory diseases.

Kinase assay

The invention provides novel methods and compositions for detecting kinase activity in solution, without the use of radioactivity. The methods marry the kinetic advantages of solution-based reaction with the efficiency and high-throughput adaptability of solid-phase wash and detection steps, yet is conveniently practiced in a single tube. The methods may be used to assay for kinase activity per se or, by controlling for the kinase activity, for modulators of kinase activity. The method is exemplified with a preferred chemiluminescent protein kinase assay using biotinylated substrate peptides captured on a streptavidin coated microtiter plate and monoclonal antibodies to detect their phosphorylation.

Gene amplification and overexpression in cancer

There are disclosed methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers in mammals, for example, humans, utilizing a gene, which is amplified in many types of cancer. The amplified gene, its expressed protein products and antibodies are used diagnostically or as targets for cancer therapy or as vaccines; they also are used to identify compounds and reagents useful in cancer diagnosis, prevention, and therapy.

IKK-β proteins, nucleic acids and methods

The invention provides methods and compositions relating to an IκB kinase, IKK-β, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-β encoding nucleic acids or purified from human cells. The invention provides isolated IKK-β hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-β genes, IKK-β-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

IRAK-4: compositions and methods of use

The present invention provides nucleic acids and polypeptides for IRAK-4, a novel member of the IRAK family of protein kinases. Members of the IRAK family are indispensable signal transducer for members of the IL-1R/Toll family of transmembrane receptors, including IL-1 receptors, IL-18 receptors and LPS receptors. IRAK-4 sequences from human and mouse are provided, as are methods for identifying compounds useful in the treatment or prevention of inflammatory diseases.

Interleukin-1 receptor accessory proteins, nucleic acids and methods

The invention provides methods and compositions relating to IL-1RAcP proteins that regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IL-1RAcP encoding nucleic acids purified from human cells. The invention provides isolated IL-1RAcP hybridization probes and primers capable of specifically hybridizing with the disclosed IL-1RAcP genes, IL-1RAcP-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Benzenesulfonamides and benzamides as therapeutic agents

The invention provides compounds, compositions and methods relating to novel aromatic derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

IKAP nucleic acids

The invention provides methods and compositions relating to IKAP proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKAP encoding nucleic acids or purified from human cells. The invention provides isolated IKAP hybridization probes and primers capable of specifically hybridizing with the disclosed IKAP genes, IKAP-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Novel receptors

The invention provides isolated nucleic acid and amino acid sequences of novel receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of the receptors.

Sitosterolemia susceptibility gene (SSG): compositions and methods of use

The present invention provides polypeptides of a novel ABC family cholesterol transporter, SSG. The herein-disclosed sequences can be used for any of a number of purposes, including for the diagnosis and treatment of cholesterol-associated disorders, including sitosterolemia, and for the identification of molecules that associate with and/or modulate the activity of SSG.

Novel G-protein coupled receptors

The invention provides isolated nucleic acid and amino acid sequences of four novel G-protein coupled receptors that are amplified in breast cancer cells, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of G-protein coupled receptors.

TRAF2-associated protein kinase and assays

The invention provides methods and compositions relating to a novel human tumor necrosis factor receptor associated factor number two associated kinase protein. The invention provides hybridization probes and primers capable of hybridizing with the disclosed gene, nucleic acids encoding the kinase, methods of making the kinase proteins, and methods of using the compositions in diagnosis and drug screening.

Nucleic acids encoding murine UCP3 genes

The invention provides methods and compositions relating to a novel family of genes, mUCP3s, involved in metabolic regulation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed mUCP3 encoding nucleic acids or purified from mammalian cells. The invention provides isolated mUCP3 hybridization probes, knock-out/in constructs and primers capable of specifically hybridizing with the disclosed mUCP3 genes, mUCP3-specific binding agents such as specific antibodies, animals and cells modified with the subject mUCP3 nucleic acids, and methods of making and using the subject compositions in the biopharmaceutical industry.

Pyrrolo[1,2-b]pyridazine derivatives

Compounds, pharmaceutical compositions and methods that are useful in the treatment or prevention of metabolic and cell proliferative diseases or conditions are provided herein. In particular, the invention provides compounds which modulate the activity of proteins involved in lipid metabolism and cell proliferation.

Combination therapeutic compositions and method of use

The present invention provides pharmaceutical compositions and methods for the treatment of diabetes mellitus using combination therapy. The compositions relate to a compound of Formula I and an antidiabetic agent such as sulfonylureas, biguanides, glitazones, α-glucosidase inhibitors, potassium channel antagonists, aldose reductase inhibitors, glucagon antagonists, activators of RXR, insulin therapy or other anti-obesity agent. The methods include the administration of the combination of compound of Formula I with antidiabetic agent where the two components are delivered in a simultaneous manner, where the compound of Formula I is administered first, followed by the antidiabetic agent, as well as wherein the antidiabetic agent is delivered first followed by the compound of Formula I.

Lometrexol combination therapy

The present invention provides compositions and methods for treating proliferative disorders using combination therapies of lometrexol and other therapeutically active agents. The methods include administration of lometrexol with one or more therapeutically active agents where lometrexol and the therapeutically active agent(s) are delivered in a single composition, where they are administered in separate compositions in a simultaneous manner, where lometrexol is administered first, followed by the therapeutically active agent(s), as well as where the therapeutically active agent(s) is delivered first, followed by lometrexol. In preferred embodiments, the therapeutically active agent(s) has antiproliferative properties.

Human NIK proteins

The invention provides methods and compositions relating to a novel kinase, NIK, involved in NFκB activation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed NIK encoding nucleic acids or purified from human cells. The invention provides isolated NIK hybridization probes and primers capable of specifically hybridizing with the disclosed NIK genes, NIK-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Antibacterial agents

Hydroxyamidines and related compounds are provided which are suitable as antibacterial agents.

IRAK3 polynucleotides

The invention provides methods and compositions relating to a novel kinase, IRAK3. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IRAK3 encoding nucleic acids or purified from human cells. The invention provides isolated IRAK3 hybridization probes and primers capable of specifically hybridizing with the disclosed IRAK3 genes, IRAK3-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Fused heterocyclic compounds

Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders.

Hydrazones and analogs as cholesterol lowering agents

Hydrazones and hydrazone analogs are provided which are useful as upregulators of LDL receptors and can be used in the treatment of hypercholesterolemia and related disorders and conditions.

Fused heterocyclic compounds

Compounds having the formula:wherein L is a bond or (C1-C4)alkylene, R'' is hydrogen or (C1-C8)alkyl, and R<1>, R<2>, R<4>, R, R', and the subscript n are as described herein, are provided, which are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. Pharmaceutical compositions and methods of using these compounds for the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor, such as eating disorders, obesity, anxiety disorders and mood disorders, are also provided.

Methods for detecting SODD genes and proteins

The invention provides methods and compositions relating to Suppressor of Death Domain (SODD) proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed SODD encoding nucleic acids or purified from human cells. The invention provides isolated SODD hybridization probes and primers capable of specifically hybridizing with the disclosed SODD genes, SODD-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Antibacterial agents

Hydroxyamidines and related compounds are provided which are suitable as antibacterial agents.

Arylsulfonanilide phosphates

The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infrections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Human telomerase gene RNA interacting protein gene

The invention provides methods and compositions relating to a human telomerase and related nucleic acids, including four distinct human telomerase subunit proteins called p140, p105, p48 and p43 having human telomerase-specific activity. The proteins may be produced recombinantly from transformed host cells from the disclosed telomerase encoding nucleic acids or purified from human cells. Also included are human telomerase RNA components, as well as specific, functional derivatives thereof. The invention provides isolated telomerase hybridization probes and primers capable of specifically hybridizing with the disclosed telomerase gene, telomerase-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Linked biaryl compounds

Compounds, compositions and methods that are useful for the treatment of metabolic disorders, inflammatory diseases and cancer are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in lipid metabolism, inflammation and cell proliferation. The subject compounds are linked biaryl compounds.

Combination therapy using pentafluorobenzenesulfonamides and antineoplastic agents

Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic agent such as gemcitabine or paclitaxel.

Novel receptors

The invention provides isolated nucleic acid and amino acid sequences of novel receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of the receptors.

Eukaryotic transcription protein; host cell factor

Host Cell Factor (HCF), a eukaryotic cellular protein involved in transcription, nucleic acids encoding HCF, and methods of using HCF and HCF-encoding nucleic acids are provided. HCF activity is disclosed to comprise a collection of polypeptides encoded by a structural gene encoding a parent protein of 2039 amino acids. HCF-specific binding compounds are disclose including antibodies to HCF epitopes. Because HCF is required for the transcription of a number of vital genes such as the immediate early genes of Herpes Simplex Virus, the invention provides HCF-based methods for screening chemical libraries for regulators of viral transcription. Such regulators are used in the treatment of viral infections by modulating the transcription of certain viral genes.

PPARgamma modulators

Modulators of PPARgamma activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

ARYLSULFONANILIDE UREAS

Pentafluorobenzenesulfonamides and analogs

The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents. The compositions include compounds of the general formula I: ...

HIV integrase inhibitors

Nitrogen-containing heteroaryl dioxo-butyric acid derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Murine UCP3 polypeptides

The invention provides methods and compositions relating to a novel family of UCP3 polypeptides and related nucleic acids involved in metabolic regulation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed mUCP3 encoding nucleic acids or purified from mammalian cells. The invention provides isolated mUCP3 hybridization probes, knock-out/in constructs and primers capable of specifically hybridizing with the disclosed mUCP3 genes, mUCP3-specific binding agents such as specific antibodies, animals and cells modified with the subject mUCP3 nucleic acids, and methods of making and using the subject compositions in the biopharmaceutical industry.

High throughput screening assays for nucleic acid ligase modulators

Screening assays for identifying ligase activity modulators are provided, in both solid phase and liquid phase formats. Solid phase formats detect ligase activity by ligating a labelled nucleic acid to a capture nucleic acid in the presence of the ligase modulator and detection of the labelled nucleic acid. Liquid phase assays detect ligation-dependent changes in interactive labels between nucleic acids such as proximity quenching of fluorescent labels. Compositions, apparatus and integrated systems for assays are also provided.

COMBINATION THERAPY USING PENTAFLUOROBENZENESULFONAMIDE AND PLATIN COMPOUND

High-throughput screening assays for modulators of nucleic acid topoisomerases

This invention provides novel assays for topoisomerase activity and for identifying topoisomerase inhibitors. The assays include both solid-phase and liquid-phase methods that are amenable to high throughput screening methods. The assays of the invention are readily adaptable to numerous types of topoisomerase, and are capable of identifying novel classes of topoisomerase activity modulators.

Novel receptors

The invention provides isolated nucleic acid and amino acid sequences of novel G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of G-protein coupled receptors.

Nucleic acid encoding an interleukin 4 signal transducer

The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by an interleukin 4 signal transducer and activator of transcription, IL-4 Stat. IL-4 Stat peptides and IL-4 receptor peptides and nucleic acids encoding such peptides find therapeutic uses. The subject compositions include IL-4 Stat and IL-4 receptor proteins, portions thereof, nucleic acids encoding them, and specific antibodies. The disclosed pharmaceutical screening methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Assays for identifying agents which affect regulators of UCP3 gene expression

The invention relates to regulators of UCP3 gene transcription, including novel UCP3 transcriptional promoters. UCP3 promoters are used in diagnosis and pharmaceutical development. In particular, transfected cells comprising UCP3 transcriptional regulators operably linked to a reporter are used in high-throughput pharmaceutical screens.

Nucleic acids encoding human NIK protein

The invention provides methods and compositions relating to a novel kinase, NIK, involved in NFκB activation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed NIK encoding nucleic acids or purified from human cells. The invention provides isolated NIK hybridization probes and primers capable of specifically hybridizing with the disclosed NIK genes, NIK-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Arylsulfonic acid salts of pyrimidine-based antiviral

Salts of pyrimidine derivatives are provided having the formula:wherein R represents hydrogen, methyl or ethyl; Z represents a substituted or unsubstituted 1-piperidinyl, a substituted or unsubstituted 4-morpholinyl, or a substituted or unsubstituted 1-pyrrolidinyl; and Ar represents a substituted or unsubstituted phenyl or a substituted or unsubstituted naphthyl. These salts are particularly useful as antiviral agents (e.g., to treat CMV infections).

Combination therapy using pentafluorobenzenesulfonamides and antineoplastic agents

Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic agent such as gemcitabine or paclitaxel.

IKK-BETA PROTEINS, NUCLEIC ACIDS AND METHODS

SODD gene expression in cancer

The invention provides methods and compositions for diagnosing and treating tumors. In particular embodiments, the invention provides methods for characterizing tumors for SODD gene copy number and/or expression and for using this diagnosis in guiding treatment options. Accordingly, the invention provides methods for biasing therapeutic options by (a) contacting a biopsy of a tumor with an agent which specifically binds a SODD gene or SODD gene product thereof; (b) measuring specific binding of the agent to the SODD gene or gene product to determine an amount of the SODD gene or gene product present in the biopsy; and (c) biasing therapeutic options for treating the tumor based on the amount of the SODD gene or gene product present in the biopsy.

IKK-β proteins, nucleic acids and methods

The invention provides methods and compositions relating to an IκB kinase, IKK-β, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-β encoding nucleic acids or purified from human cells. The invention provides isolated IKK-β hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-β genes, IKK-β-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

PPARgamma modulators

Modulators of PPARγ activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

Detection method for monitoring beta tubulin isotype specific modification

This invention relates to monoclonal antibodies that recognize modified β-tubulin isotypes, methods of using such antibodies to detect modified β-tubulin isotypes, methods of using such antibodies to monitor β-tubulin modifying agents administered to a patient, methods of using such antibodies to isolate modified β-tubulin, and methods of detecting the anti-modified β-tubulin antibodies.

PPAR-gamma modulators

Modulators of PPARgamma activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

CXCR3 antagonists

Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.

Ccr4 antagonists

Compounds, compositions and methods are provided that are useful in the treatment of chemokine receptor-mediated conditions and diseases. In particular, the invention provides compounds which modulate CCR4 function or a CCR4-mediated response. The subject compounds and compositions are useful for the treatment or prevention of inflammatory conditions and diseases.

Arylsulfonanilide ureas

The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

IκB kinases

The invention provides methods and compositions relating to IκB regulating proteins, known as T2K proteins, and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed T2K encoding nucleic acid or purified from human cells. The invention provides specific hybridization probes and primers capable of specifically hybridizing with the disclosed T2K gene, T2K-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

PRC17: an amplified cancer gene

The present invention provides nucleic acid and protein sequences for a novel protein, PRC17, and methods, reagents, and kits for diagnosing and treating cancer in a mammal, e.g., a human. This invention is based upon the discovery that the novel PRC17 is overexpressed and/or amplified in cancer. Methods to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and to treat cancer, by inhibiting the expression and/or activity of PRC17 in a cancer cell are included.

Compounds for the modulation of PPARgamma activity

Modulators of PPARγ activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

Diagnosis and treatment of cancer using mammalian pellino polypeptides and polynucleotides

The present invention provides methods, reagents, and kits for diagnosing and treating cancer in a mammal, e.g., a human. This invention is based upon the discovery that Pellino 1 or 2 is overexpressed and/or amplified in cancer. Methods to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and to treat cancer, by inhibiting the expression and/or activity of Pellino 1 or 2 in a cancer cell are included.

Benzenesulfonamides and benzamides as therapeutic agents

The invention provides compounds, compositions and methods relating to novel aromatic derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

UCP3 genes

The invention provides methods and compositions relating to a novel family of UCP3 polypeptides and related nucleic acids involved in metabolic regulation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed mUCP3 encoding nucleic acids or purified from mammalian cells. The invention provides isolated mUCP3 hybridization probes, knock-out/in constructs and primers capable of specifically hybridizing with the disclosed mUCP3 genes, mUCP3-specific binding agents such as specific antibodies, animals and cells modified with the subject mUCP3 nucleic acids, and methods of making and using the subject compositions in the biopharmaceutical industry.

IKK-alpha proteins nucleic acids and methods

The invention provides methods and compositions relating to an IkappaB kinase, IKK-alpha, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-alpha encoding nucleic acids or purified from human cells. The invention provides isolated IKK-alpha hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-alpha genes, IKK-alpha-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Gene amplification and overexpression in cancer

There are disclosed methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers in mammals, for example, humans, utilizing a gene, which is amplified in many types of cancer. The amplified genes, their expressed protein products and antibodies are used diagnostically or as targets for cancer therapy or as vaccines; they also are used to identify compounds and reagents useful in cancer diagnosis, prevention, and therapy.

Heterocyclic arylsulfonamidobenzylic compounds

Heterocyclic arylsulfonamidobenzylic compounds are provided which are useful in treating lipid disorders, metabolic disorders and cell-proliferative diseases.

Arylsulfonanilide ureas

The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Suppressors of death domains

The invention provides methods and compositions relating to Suppressor of Death Domain (SODD) proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed SODD encoding nucleic acids or purified from human cells. The invention provides isolated SODD hybridization probes and primers capable of specifically hybridizing with the disclosed SODD genes, SODD-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Linked biaryl compounds

Compounds, compositions and methods that are useful for the treatment of metabolic disorders, inflammatory diseases and cancer are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in lipid metabolism, inflammation and cell proliferation. The subject compounds are linked biaryl compounds.

Imidazole derivates as anti-inflammatory agents

Compounds (I), pharmaceutical compositions thereof are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. All definitions are as in the application.

Arylsulfonanilide ureas

The invention provides compounds, compositions and methods relating to arylsulfonanilide derivatives having the formula (I) or a pharmaceutically acceptable salt thereof, wherein Ar is a member selected from the group consisting of (a), (b), (c), and (d) and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Methods of assaying for compounds that inhibit premature translation termination and nonsense-mediated rna decay

The present application provides methods of assaying for compounds that inhibit premature translation termination and nonsense mediated RNA decay in cells.

Lxr modulators

The invention provides compounds, compositions and methods for modulating the effects of LXR in a cell. The compounds and compositions are useful both as diagnostic indicators of LXR function and as pharmacologically active agents. The compounds and compositions find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.

Inflammation modulators

Tubulin-binding agents

Derivatives of known tubulin-binding compounds are provided in which a (poly)fluorobenzene, a fluoropyridine, or a fluoronitrobenzene moiety is incorporated or added to the structure. These derivatives can be used as antimitotic agents and can be considered covalent modifiers of tubulin. The strategy developed for each of the compounds is to i) append a fluorinated electrophile (e.g., pentafluorophenylsulfonamido, 2-fluoropyridyl, or 3,5-dinitro-4-fluorophenyl) to an existing functional group in a natural product, ii) replace an aromatic ring in a natural product with a fluorinated electrophile, or iii) attach a fluorinated electrophile to an open valence in a portion of the molecule that will not interfere with recognition and binding to the tubulin site. Derivatives are provided based on colchicine, steganacin, podophyllotoxin, nocodazole, combretastatin, curacin A, vinblastine, vincristine, dolastatin, 2-methoxyestradiol, dihydroxy-pentamethoxyflavanone and others.

Ureias de arilsulfonanilida

Pentafluorobenzenossulfonamidas e analogos

Pentafluorobenzenosulfonamidas e analogos

Compound, composition and method for preventing or suppressing a viral infection

"COMPOSTO, COMPOSIçãO E MéTODO PARA PREVENçãOOU SUPRESSãO DE UMA INFECçãO VIRAL". Composto ecomposição que são usados para o tratamento de infecções virais,particularmente infecções de citomegalovirus humano. Oscompostos incluem novos derivados a base de pirimidina tendo afórmula (I) onde X é um membro selecionado do grupo que consistede -NR^ 3^R^ 4^, -OR^ 3^ -SR^ 3^, arila, alquila e arilalquila; Y éum membro selecionado do grupo que consiste de uma ligaçãocovalente, -N(R^ 6^)-, -O-, -S-, -C(=O)- e alquileno; R^ 1^ e R^ 2^são membros independentemente selecionados do grupo queconsiste de hidrogênio, alquila, -O-alquila, -S-alquila, arila,arilalquila, -O-arila, -S-arila, -NO~ 2~, -NR^ 7^R^ 8^, -C (0) R^ 9^,-CO~ 2~R^ 10^, -C(O)NR^ 7^R^ 8^, -N(R^ 7^) C (0) R^ 9^, -N(R^ 7~) CO~ 2~R^ 11^, N (R^ 9^) C (0) NR^ 7^R^ 8^, -S (0)~m~NR^ 7^R^ 8^, -S(O)~ n~R^ 9^, -CN, halogênio, e -N(R^ 7^) S(0)~ m~R^ 11^.

Modulation of ccr4 function

Compounds and compositions are provided that bind to the CCR4 chemokine receptor and which are useful for treating diseases associated with CCR4 activity, such as contact hypersensitivity.

Methods of using pyrimidine-based antiviral agents

Nuclear factors and binding assay

The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by a transcription complex containing at least a human nuclear factor of activated T-cells (hNFAT). The materials include a family of hNFAT proteins, active fragments thereof, and nucleic acids encoding them. The methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

High-throughput screening assays for modulators of nucleic acid topoisomerases

This invention provides novel assays for topoisomerase activity and for identifying topoisomerase inhibitors. The assays include both solid-phase and liquid-phase methods that are amenable to high throughput screening methods. The assays of the invention are readily adaptable to numerous types of topoisomerase, and are capable of identifying novel classes of topoisomerase activity modulators.

Anti-viral pyrimidine derivs

本发明揭示了用于治疗病毒感染,特别是巨细胞病毒感染的化合物和组合物。化合物包括新颖的基于嘧啶的衍生物,它具有式(Ⅰ)结构,其中X选自－NR 3 R 4 、－OR 3 、－SR 3 、芳基、烷基和芳基烷基;Y选自共价键、－N(R 6 )－、－O－、－S－、－C(=O)－和亚烷基;R 1 和R 2 独立地选自氢、烷基、－O－烷基、－S－烷基、芳基、芳基烷基、－O－芳基、－S－芳基、－NO 2 、－NR 7 R 8 、－C(O)R 9 、－C(O) 2 R 10 、－C(O)NR 7 R 8 、－N(R 7 )C(O)R 9 、－N(R 7 )CO 2 R 11 、－N(R 9 )C(O)NR 7 R 8 、－S(O) m NR 7 R 8 、－S(O) n R 9 、－CN、卤素和－N(R 7 )S(O) m R 11 。

Amplified gene involved in cancer

There are disclosed methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers in mammals, for example, humans, utilizing the C8FW gene, which are amplified breast and/or brain and/or colon and/or lung and/or prostate and/or ovarian cancer genes. The C8FW gene, its expressed protein products and antibodies are used diagnostically or as targets for cancer therapy or vaccine; they are also used to identify compounds and reagents useful in cancer diagnosis, prevention, and therapy.

Amplified oncogenes and their involvement in cancer

There are disclosed methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers in mammals such as humans, utilizing the Galanin, Galanin Receptor 2 (GALR2) and Galanin Receptor 3 (GALR3) genes, which are amplified in breast and/or lung and/or brain and/or colon and/or prostate and/or ovarian cancer genes. The Galanin, GALR2 and GALR3 genes and their expressed protein products and antibodies are used diagnostically or as targets for cancer therapy or vaccine; they are also used to identify compounds and reagents useful in cancer diagnosis, prevention, and therapy. There is also disclosed a GALR2-GALR3 heterocomplex formation during tumorigenesis.

Gene amplification and overexpression in cancer

There are disclosed methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers in mammals, for example, humans, utilizing the MKPX gene, which are amplified colon and/or ovarian and/or prostate cancer genes. The MKPX gene, its expressed protein products and antibodies are used diagnostically or as targets for cancer therapy or vaccine; they are also used to identify compounds and reagents useful in cancer diagnosis, prevention, and therapy.

Imidazole derivates as antiinflammatory agents

Irak-4: compositions and methods of use

The present invention provides nucleic acids and polypeptides for IRAK-4, a novel member of the IRAK family of protein kinases. Members of the IRAK family are indispensable signal transducer for members of the IL-1R/Toll family of transmembrane receptors, including IL-1 receptors, IL-18 receptors and LPS receptors. IRAK-4 sequences from human and mouse are provided, as are methods for identifying compounds useful in the treatment or prevention of inflammatory diseases.

Interleukin-1 receptor-associated protein kinase and assays

The invention relates to human Interleukin-1 Receptor-Associated Protein Kinases (IRAKs), nucleic acids which encode IRAKs and hybridization probes and primers capable of hybridizing with IRAK genes and methods of using the subject compositions; in particular, methods such as IRAK-based in vitro binding assays and phosphorylation assays for screening chemical libraries for lead compounds for pharmacological agents.

Benzimidazole derivatives

Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. The subject compounds are 2-amino-imidazole derivatives.

Imidazole derivates as anti-inflammatory agents

Compounds (I), pharmaceutical compositions thereof are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate th e expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. All definitions are as in the application.

Imidazole derivatives as antiinflammatory agents

Compounds (I), pharmaceutical compositions thereof are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. All definitions are as in the application.

CXCR3 antagonists

Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.

Modulation of ccr4 function

Compounds and compositions are provided that bind to the CCR4 chemokine receptor and which are useful for treating diseases associated with CCR4 activity, such as contact hypersensitivity.

Pyrimidine derivatives

Compounds and compositions are provided which are useful for the treatment of viral infections, particularly human Cytomegalovirus infection. The compounds include novel pyrimidine-based derivatives.

Pyrimidine derivatives

Compounds and compositions are provided which are useful for the treatment of viral infections, particularly human Cytomegalovirus infection. The compounds include novel pyrimidine-based derivatives.

Cxcr3 antagonists

本发明提供用于治疗炎症和免疫症状和疾病的化合物、组合物和方法。特别是，本发明提供调节趋化因子受体表达和/或功能的化合物。所述方法用于治疗炎症以及免疫调节紊乱和疾病如多发性硬化、类风湿性类节炎和I型糖尿病。

Combination therapy using pentafluorobenzenesulfonamide

提供了治疗增殖异常的综合疗法,它使用式(I)的五氟苯磺酰胺和抗肿瘤性铂配位复合物,如顺氯氨铂。

Human telomerase RNA interacting protein gene

The invention provides methods and compositions relating to a human telomerase and related nucleic acids, including four distinct human telomerase subunit proteins called p140, p105, p48 and p43 having human telomerae-specific activity. The proteins may be produced recombinantly from transformed host cells from the disclosed telomerase encoding nucleic acids or purified from human cells. Also included are human telomerase RNA components, as well as specific, functional derivative thereof. The invention provides isolated telomerase hybridization probes and primers capable of specifically hybridizing with the disclosed telomerase gene, telomerase-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Irak-4: compositions and methods of use

The present invention provides nucleic acids and polypeptides for IRAK-4, a novel member of the IRAK family of protein kinases. Members of the IRAK family are indispensable signal transducer for members of the IL-1R/Toll family of transmembrane receptors, including IL-1 receptors, IL-18 receptors and LPS receptors. IRAK-4 sequences from human and mouse are provided, as are methods for identifying compounds useful in the treatment or prevention of inflammatory diseases.

Lxr modulators

The invention provides compounds, compositions and methods for modulating the effects of LXR in a cell. The compounds and compositions are useful both as diagnostic indicators of LXR function and as pharmacologically active agents. The compounds and compositions find particular use in the treatment of disease states associated with cholesterol metabolism, particularly atherosclerosis and hypercholesterolemia.

TRAF Inhibitors

The invention concerns novel inhibitors of tumor necrosis factor receptor associated factor(TRAF) mediated signal transduction. The invention encompasses the novel inhibitor proteins (I-TRAFs), nucleic acid encoding them, methods for their recombinant production, and their use in screening assays and as pharmaceuticals.

Identification of an amplified gene and target for drug intervention

Novel receptors

The invention provides isolated nucleic acid and amino acid sequences of novel receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of the receptors.

Pentafluorobenzenesulfonamides and analogs

The invention provides methods and compositions relating to novel pentafluorobenzenesulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents. The compositions include compounds of general formula (I).

Kinase assay

The invention provides novel methods and compositions for detecting kinase activity in solution, without the use of radioactivity. The methods marry the kinetic advantages of solution-based reaction with the efficiency and high-throughput adaptability of solid-phase wash and detection steps, yet is conveniently practiced in a single tube. The methods may be used to assay for kinase activity per se or, by controlling for the kinase activity, for modulators of kinase activity. The method is exemplified with a preferred chemiluminescent protein kinase assay using biotinylated substrate peptides captured on a streptavidin coated microtiter plate and monoclonal antibodies to detect their phosphorylation.

Fused heterocyclic compounds

Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders.

Interleukin 4 signal transducers and binding assays

The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by an interleukin 4 signal transducer and activator of transcription, IL-4 Stat. IL-4 Stat peptides and IL-4 receptor peptides and nucleic acids encoding such peptides find therapeutic uses. The subject compositions include IL-4 Stat and IL-4 receptor proteins, portions thereof, nucleic acids encoding them, and specific antibodies. The disclosed pharmaceutical screening methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Bisphenylsulfanyl and sulphonate compounds and use thereof for elevating hdl cholesterol levels

Provided herein are compounds and compositions that modulate the type 6 peroxisome proliferator-activated receptor (PPAR.sigma.). The subject compounds have the formula R1O2C-CR a R b-Y Ar1-X-Ar2-Z1-Z2-Ar3 wherein X is S(O)m, where the subscript m is an integer from 0 to 2; Y is 0; Z1 and Z2 are independently selected from the group consisting of O, (CR'R")n, and N(R"), where the subscript n is an integer from 1 to 2 and each R' and R" is hydrogen; Ar1 and Ar2 are independently naphthyl or phenyl, optionally substituted by halogen, and (C1-C4)alkyl; Ar3 is phenyl substituted by trifluoromethyl; R1 is hydrogen; and R a and R b are each hydrogen, or pharmaceutically acceptable salts thereof. Uses of the compounds and compositions, for instance, to treat a condition or disorder responsive to PPAR.sigma. modulation, such as hypercholesterolemia, among other conditions or disorders, or to elevate high density lipoprotein (HDL) cholesterol levels, are also provided herein.

Traf inhibitors

The invention concerns novel inhibitors of tumor necrosis factor receptor associated factor-(TRAF) mediated signal transduction. The invention encompasses the novel inhibitor proteins (I-TRAFs), nucleic acid encoding them, methods for their recombinant production, and their use in screening assays and as pharmaceuticals.

IKK-beta proteins, nucleic acids and methods

Human transcription factors and binding assays

The invention provides methods and compositions for identifying pharmacological agents useful in the diagnosis or treatment of disease associated with the expression of a gene modulated by a transcription complex containing at least a human nuclear factor of activated T-cells (hNFAT). The materials include a family of hNFAT proteins, active fragments thereof, and nucleic acids encoding them. The methods are particularly suited to high-throughput screening where one or more steps are performed by a computer controlled electromechanical robot comprising an axial rotatable arm.

Ikb kinases

The invention provides methods and compositions relating to IB regulating proteins, known as T2K proteins, and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed T2K encoding nucleic acid or purified from human cells. The invention provides specific hybridization probes and primers capable of specifically hybridizin g with the disclosed T2K gene, T2K-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Irak-4: compositions and methods of use

The present invention provides nucleic acids and polypeptides for IRAK-4, a novel member of the IRAK family of protein kinases. Members of the IRAK family are indispensable signal transducer for members of the IL-1R/Toll family of transmembrane receptors, including IL-1 receptors, IL-18 receptors and LPS receptors. IRAK-4 sequences from human and mouse are provided, as are methods for identifying compounds useful in the treatment or prevention of inflammatory diseases.

Uncoupling protein-2(hcp2): compositions and methods of use

The present invention relates generally to compositions and methods for the treatment of body weight disorders including, but not limited to, obesity. More specifically, the present invention relates to nucleic acids encoding a human UCP2 polypeptide; a human UCP2 polypeptide encoded by such nucleic acids; recombinant nucleic acid molecules containing nucleic acids encoding a human UCP2 polypeptide; cells containing such recombinant nucleic acid molecules; a method for producing human UCP2 polypeptides; and methods for detecting modulators of UCP2 gene expression and UCP2 polypeptide expression.

Substituted benzene compounds as antiproliferative and cholesterol lowering agents

The invention provides compounds, compositions and methods relating to novel electrophilic aromatic derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents. The compositions include compounds of general Formula (I).

UCP3 genes

Arylsulfonanilide ureas

本发明提供了有关具有式Ⅰ的芳基磺酰基苯胺衍生物或其药学上可接受的盐的化合物、组合物和方法，以及它们作为药理学活性剂的用途，其中Ar选自(a)、(b)、(c)和(d)之一。发现了所述的组合物在疾病尤其是癌症、牛皮癣、血管的再狭窄(restenosis)、传染病、动脉粥样硬化和高胆固醇血症的治疗中作为药理学试剂或者作为开发这种药理学试剂的导向化合物的特殊用涂。

Pentafluorobenzenesulfonamides and analogs

The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents. The compositions include compounds of the general formula I:

Pentafluorobenzenesulfonamides and analogs

The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, vascular restenosis, microbial infections, and psoriasis, or as lead compounds for the development of such agents. The compositions include compounds of general formula (I).

Compound exhibiting CXCR3 antagonistic activity and pharmaceutical preparation

Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.

Antibacterial agents

Hydroxyamidines and related compounds are provided which are suitable as antibacterial agents.

IKK-β proteins, nucleic acids and methods

The invention provides methods and compositions relating to an IκB kinase, IKK-β, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-β encoding nucleic acids or purified from human cells. The invention provides isolated IKK-β hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-β genes, IKK-β-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

IkB kinases

Anti-viral pyrimidine derivatives

Compounds and compositions are provided which are useful for the treatment of viral infections, particularly human Cytomegalovirus infection. The compounds include novel pyrimidine-based derivatives.

Human and mouse g-protein couipled receptors

The invention provides isolated nucleic acid and amino acid sequences of novel receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of the receptors.

Methods for the diagnosis and treatment of tumors employing the hepsin gene

I-(kappa)- b(kinases)

The invention provides methods and compositions relating to IλB regulating proteins, known as T2K proteins, and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed T2K encoding nucleic acid or purified from human cells. The invention provides specific hybridization probes and primers capable of specifically hybridizing with the disclosed T2K gene, T2K-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Diagnosis and treatment of cancer using star polypeptides and polynucleotides

Modulators of the constitutive adrostane receptor (car): screening and treatment of hypercholesterolemia

This invention provides methods that are useful for identifying therapeutic agents for the treatment of a CAR-mediated disorder or condition. The methods include determining whether the candidate therapeutic agent can: interact directly with CAR, modulate CAR-mediated gene expression, decrease CAR antagonist elevation of a cholesterol indicator in a mammal, or decrease a cholesterol level indicator in a mammal with a defective CAR. Also provided are CAR agonists.____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Combination therapy using pentafluorobenzenesulfonamides

Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula (I) and an antineoplastic platinum coordination complex such as cisplatin.

Kcnb: a novel potassium channel protein

The present invention provides nucleic acid and protein sequences for a novel potassium channel protein, KCNB. The herein-disclosed sequences can be used for any of a number of purposes, including for the specific detection of KCNB, for the identification of molecules that associate with and/or modulate the activity of KCNB, to diagnose any of a number of conditions associated with KCNB or KCNB activity, or to modulate the number or activity of KCNB molecules in a mammal.

Nik proteins, nucleic acids and methods

The invention provides methods and compositions relating to a novel kinase, NIK, involved in NF.kappa.B activation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed NIK encoding nucleic acids or purified from human cells. The invention provides isolated NIK hybridization probes and primers capable of specifically hybridizing with the disclosed NIK genes, NIK-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Substituted benzene compounds as antiproliferative and cholesterol lowering agents

The invention provides compounds, compositions and methods relating to novel electrophilic aromatic derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents. The compositions include compounds of general Formula (I).

Pyrazole antimicrobial agents

The present invention provides pyrazole and pyrazolone derivatives. Preferred compounds of the invention are useful as RNA polymerase inhibitors. Further preferred compounds of the invention are useful as antimicrobial agents.

DIAGNOSIS AND TREATMENT OF CANCER USING StAR POLYPEPTIDES AND POLYNUCLEOTIDES

The present invention provides methods, reagents, and kits for diagnosing and treating cancer in a mammal, e.g., a human. This invention is based upon the surprising discovery that the StAR gene is overexpressed and/or amplified in a number of types of cancer cells. Accordingly, the present methods can be used to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and to treat cancer, e.g., by inhibiting the expression and/or activity of StAR in a cancer cell.

Interleukin 4 signal transducers and binding assays

Nik proteins, nucleic acids and methods

The invention provides methods and compositions relating to a novel kinase, NIK, involved in NF.kappa.B activation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed NIK encoding nucleic acids or purified from human cells. The invention provides isolated NIK hybridization probes and primers capable of specifically hybridizing with the disclosed NIK genes, NIK-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Pentafluorobenzenesulfonamides and analogs

Use of a farnesoid x receptor antagonist for treating hyperlipidemia

The present invention provides a therapeutic agent for hyperlipidemia, which has a novel action mechanism and which contains a farnesoid X receptor (FXR) antagonist as an active ingredient, and a screening method of the antagonist.

Cxcr3 antagonists

Compounds for the modulation of PPARgamma activity

Disclosed are compounds of the formula (I): wherein Ar1 is a substituted or unsubstituted naphthyl, X is a divalent linkage selected from the group consisting of alkylene, alkylenoxy, alkylenamino, alkylene-S(O)--k-, -O-, -C(O)-, -N(R11)-, -N(R11)C(O)-, S(O)k- and a single bond, wherein and the subscript k is an integer of from 0 to 2; Y is a divalent linkage selected from the group consisting of alkylene, -O-, -C(O)-, -N(R12)-S(O)m-, -N(R12)-S(O)m-, -N(R12)-S(O)m-N(R13)-, -N(R12)C(O), -S(O)n- and a single bond, wherein -NiR' -S(O) and a single bond, wherein subscripts m and n are integers of from 0 to 2; R1 is a member selected from the group consisting of H, heteroalkyl, aryl, arylalkyl, halogen, cyano, nitro, alkyl, alkoxy, -C(O)R14, -CO2R14, -C(O)NR14R15, -S(O)p-R14, -S(O)q-, NR15R16, -O-C(O)-OR17, -O-C(O)-R17, -O-C(O)-NR15R16, N(R14)-C(O)-NR15R16, -N(R14)-C(O)-R17 and N(R14)-C(O)-OR17; R2 is a substituted or unsubstituted aryl; and R3 is a member selected from the group consisting of halogen, cyano, nitro, and alkoxy. Further disclosed is the use of compounds of the formula (I) in the preparation of a medicament for modulating conditions associated with metabolic or inflammatory disorders; disorders mediated by PPARgamma; and disorders selected from the group consisting of NIDDM, obeisity, hypercholesterolemia and other lipid mediated diseases and inflammatory conditions. (62) Divided out of 516455

Transcription factor-dna binding assay

Pharmacological agents active at the level of gene transcription are identified in high throughput drug screening assays. The methods involve combining a labeled transcription factor, a nucleic acid coupled to a ligand, a candidate pharmacological agent and a receptor immobilized on a solid substrate, such as a microtiter plate, filter, or bead. The nucleic acid has at least that portion of a nucleotide sequence naturally involved in the regulation of the transcription of the gene which is necessary for sequence-specific interaction with the transcription factor. The resultant combination is incubated under conditions whereby the receptor is bound to the ligand and, but for the presence of said candidate pharmacological agent, the transcription factor is sequence-specifically bound to the nucleic acid. Unbound transcription factor is then removed or washed from the solid substrate and labelled, sequence-specifically bound transcription factor is detected. Incubates which include candidate agents which alter transcription factor binding deviate from control incubates in terms of label signal - typically, binding is disrupted and the signal is diminished. In a preferred embodiment, the entire process is performed by a computer-controllable electromechanical robot with an axial rotatable arm.

High-throughput screening assays for modulators of nucleic acid topoisomerases

Combination therapy using pentafluorobenzenesulfonamide and platin compound

Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic platinum coordination complex such as cisplatin.

Regulators of UCP2 gene expression

Heterocyclic arylsulfonamidobenzylic compounds

Heterocyclic arylsulfonamidobenzylic compounds are provided which are useful in treating lipid disorders, metabolic disorders and cell-proliferative diseases.

Traf Inhibitors.

Traf2-associated protein kinase and assays

A novel retinal nuclear hormone receptor

Antiinflammation agents

Compounds, compositions and methods that are useful in the treatment of inflammatory, immunoregulatory, metabolic and cell proliferative conditions or diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, metabolism and cell proliferation. The subject compounds contain fused carbocyclic or heterocyclic rings.

A high-throughput screening assay for inhibitors of nucleic acid polymerases

The invention provides promoter specific and promoter non-specific screening assays for identifying an inhibitor of a pathogenic nucleic acid polymerase activity, e.g., an RNA polymerase derived from a phatogenic infectious organism such as a bacterium, protozoan or fungus. Generally, the methods involve forming a mixture of nucleotide, a polynucleotide template, a pathogenic polymerase, and a candidate inhibitor of polymerase activity, where at least one of the nucleotide comprises a detectable label. In a preferred embodiment, a membrane apparatus (10) having two filters extending transversely across a well, and positioned between the top, tube containing half (11) of the apparatus (10) and the bottom, drip director containing half (15) of the apparatus (10). The top filter (13) is initially hydrophobic and capable of retaining liquid media and is rendered water permeable by contacting it with an organic solvent. The bottom filter (14) is hydrophilic water permeable and efficiently passes liquid media while retaining micro-beads during vacuum filtration.

SUBSTITUTED BENZENE COMPOUNDS AS AN ANTIPROLIFERATIVE AGENT

Amplified gene involved in cancer

There are disclosed methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers in mammals, for example, humans, utilizing the C8FW gene, which are amplified breast and/or brain and/or colon and/or lung and/or prostate and/or ovarian cancer genes. The C8FW gene, its expressed protein products and antibodies are used diagnostically or as targets for cancer therapy or vaccine; they are also used to identify compounds and reagents useful in cancer diagnosis, prevention, and therapy.

Antiviral agents

The transcriptional promoter of the obesity gene

The invention relates to the Ob gene transcriptional promoter. The subject promoters generally comprise a C/EBP binding site and a novel untranslated Ob gene exon. Ob gene promoters are used in diagnosis and pharmaceutical development. In particular, transfected adipocytes comprising Ob gene promoters operably linked to a reporter are used in high-throughput pharmaceutical screens.