Methods and systems for populating and searching a drug informatics database

The present invention provides a method for populating and searching a drug informatics database that includes receiving unprocessed data associated with a chemical compound from one or more data sources. The unprocessed data is parsed into a plurality of data objects based on a categorization associated with each of the data objects. Additional information, such as explanatory notes, is identified and associated with at least one of the data objects. The data objects are stored in entries within a data structure, where the data structure is searchable based on one or more of the data objects. A query for data associated with a chemical compound is received at a drug informatics database. The drug informatics database is then searched for data associated with the chemical compound and the search results are provided to a user.

Small molecule inhibitors of XBP1 splicing

Small molecule inhibitors of XBP1 splicing by IRE1α are provided, as well as methods for their use in treating or preventing cancer (e.g., endocrine resistant breast cancer), diabetes, and obesity.

Specific inhibitors for vascular endothelial growth factor receptors

The present application describes isoindoles and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful inhibitors of VEGFR.

CADHERIN-11 INHIBITORS AND METHODS OF USE THEREOF

Cadherin-11 inhibitors and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis.

Predicting drug-target interactions and uses for drug repositioning and repurposing

Described herein are methods of predicting drug-target interactions and methods of using the information for drug repurposing. The methods described herein combine different descriptors, including, for example, atom pair similarity, shape, topology and chemical signatures, physico-chemical functional descriptors, contact points of the ligand and the target protein, chemical similarity, and docking score.

Substituted pyrazines as cadherin-11 inhibitors

This invention provides for a method of preventing or treating a cadherin-11 related disease in a subject, which includes administering to the subject an effective amount of a compound of the following formula: or a pharmaceutically acceptable salt or prodrug thereof, where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, X1 and X2 are as defined herein.

Cadherin-11 Inhibitors and Methods of Use Thereof

Cadherin-11 inhibitors and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis. 2. The compound of claim 1 , wherein Ris hydroxyl.3. The compound of claim 1 , wherein Ris chloro.4. The compound of claim 1 , wherein Ris hydroxyl.5. The compound of claim 1 , wherein Ris hydroxyl claim 1 , chloro claim 1 , or carboxyl.13. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.14. A method of preventing or treating a cadherin-11 related disease in a subject claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject an effective amount of a compound of .'}17. The method of claim 14 , wherein the cadherin-11 related disease is rheumatoid arthritis.18. The method of claim 14 , wherein the cadherin-11 related disease is a cancer.19. The method of claim 18 , wherein the cancer is breast cancer claim 18 , prostate cancer claim 18 , glioma claim 18 , glioblastoma claim 18 , myeloma claim 18 , leukemia claim 18 , a poor prognosis or invasive cancer claim 18 , a basal-like cancer claim 18 , a mesenchymal-like cancer claim 18 , or metastatic cancer.20. The method of claim 14 , wherein the method further comprises administering a second therapeutic agent to the subject.21. The method of claim 20 , wherein the second therapeutic agent is a chemotherapeutic agent or an anti-inflammatory agent. This application is a continuation of U.S. application Ser. No. 14/323,374, filed Jul. 3, 2014, which is currently pending and which is a continuation of U.S. application Ser. No. 13/148,579, filed Feb. 8, 2012, now issued U.S. Pat. No. 8,802,687, which is a U.S. national stage filing of PCT/US10/23556, filed Feb. 9, 2010, which claims priority to U.S. Provisional Application No. 61/151,038, filed Feb. 9, 2009. These applications are incorporated by reference herein in their entireties.This invention ...

METHODS FOR MODULATING PLANT RESPONSE TO ENVIRONMENTALLY-INDUCED STRESS

Compounds and methods are described herein that are effective to modulate plant response (e.g., plant susceptibility) to environmentally-induced stress. The compounds and methods described herein advantageously may be used to modulate environmental stress resistance in a wide variety of plants. Environmental stresses include, for example, high light intensity (UV exposure), temperature (e.g., high heat), high soil salinity, and low soil moisture (e.g., drought). As used herein, environmental stresses include any conditions that result in increased generation of reactive oxygen species (ROS) and accumulation of ROS in the plant cells. The compounds described herein that are effective to modulate resistance to the stress prevent, directly or indirectly, or increase phosphorylation of Tyr 248 of the RACK1A protein.

Cadherin-11 Inhibitors and Methods of Use Thereof

Cadherin-11 inhibitors and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. A composition comprising a compound of and a pharmaceutically acceptable carrier.13. (canceled)15. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)24. (canceled)26. (canceled)27. (canceled)28. (canceled)31. The method of claim 14 , wherein the cadherin-11 related disease is rheumatoid arthritis.32. The method of claim 14 , wherein the cadherin-11 related disease is a cancer.33. The method of claim 32 , wherein the cancer is breast cancer claim 32 , prostate cancer claim 32 , glioma claim 32 , glioblastoma claim 32 , myeloma claim 32 , leukemia claim 32 , a poor prognosis or invasive cancer claim 32 , a basal-like cancer claim 32 , a mesenchymal-like cancer claim 32 , or metastatic.34. (canceled)35. (canceled)36. (canceled)37. (canceled)38. (canceled)39. (canceled)40. (canceled)41. (canceled)42. (canceled)43. The method of claim 14 , wherein the method further comprises administering a second therapeutic agent to the subject.44. The method of claim 43 , wherein the second therapeutic agent is a chemotherapeutic agent or an anti-inflammatory agent.45. (canceled)46. A method of preventing or treating cancer in a subject claim 43 , comprising:a) selecting a subject with a poor prognosis cancer; andb) administering to the subject a cadherin-11 inhibitor.47. (canceled)48. The method of claim 46 , wherein the cadherin-11 inhibitor is an antibody. This application is a continuation of U.S. application Ser. No. 13/148,579, filed Feb. 8, 2012, which is currently pending and which is a U.S. national stage filing of PCT/US10/23556, filed Feb. 9, 2010, which claims priority to U.S. Provisional Application No. 61/151,038, filed Feb. 9, 2009. These ...

SPECIFIC INHIBITORS FOR VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTORS

The present application describes isoindoles and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful inhibitors of VEGFR.

Cadherin-11 inhibitors and methods of use thereof

Cadherin-11 inhibitors and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis.

TREATING MELANOMA WITH MEBENDAZOLE AND A MITOGEN-ACTIVATED KINASE INHIBITOR

Provided herein are methods for treating melanoma in a subject.

SMALL MOLECULE INHIBITORS OF AGBL2

Small molecule inhibitors of AGBL2 are provided, as well as methods of using the inhibitors to treat or prevent cancer and neurologic disorders. 2. The compound of claim 1 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.6. The compound of claim 5 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.1110. A composition comprising a compound of any of - and a pharmaceutically acceptable carrier.13. The method of claim 12 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.17. The method of claim 16 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.2322. The method of any of - claims 1 , further comprising administering a second therapeutic agent to the subject.24. The method of claim 23 , wherein the second therapeutic agent is a chemotherapeutic agent.26. The method of claim 25 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.30. The method of claim 29 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.3635. The method of any of - claims 25 , further comprising administering a second therapeutic agent to the subject.37. The method of claim 36 , wherein the second therapeutic agent is an anti-depressant or an anxiolytic. This application claims priority to U.S. Provisional Application No. 61/443,069, filed Feb. 15, 2011, which is incorporated herein by reference in its entirety.The removal of the C-terminal tyrosine of α-tubulin to form detyrosinated α-tubulin is involved in several aspects of microtubule function, including kinesin interactions, spindle dynamics, mitosis, and neuronal specification. Microtubules containing large amounts of detyrosinated α-tubulin are more stable and resistant to depolymerization by destabilizing agents. Further, detyrosinated α-tubulin has been shown to be elevated in aggressive breast and prostate cancers.Provided herein are small molecule inhibitors of ATP/GTP binding protein ...

VASCULAR ENDOTHELIAL RECEPTOR SPECIFIC INHIBITORS

The present application describes isoindoles and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful inhibitors of VEGFR.

SPECIFIC INHIBITORS FOR VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTORS

The present application describes isoindoles and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful inhibitors of VEGFR.

Cadherin-11 inhibitors and methods of use thereof

Cadherin-11 inhibitors, including 4-(2-phenylpyridin-3-yl)phenol, and methods for the prevention and treatment of cadherin-11 related diseases are described herein. Cadherin-11 related diseases include cancer and rheumatoid arthritis.

APPARATUS AND METHODS TO REMOVE TOXINS FROM BLOOD BY PLASMAPHERESIS

Devices and method are provided for removing toxins, including protein-bound toxins, from blood. The device includes a housing having a receiving space and at least one hollow fiber extending through at least a portion of the receiving space. The at least one hollow fiber is operable to receive the stream of blood. The device further includes a plurality of beads disposed within the receiving space and external to the at least one hollow fiber. The at least one hollow fiber includes a plurality of pores operable to retain the one or more cellular elements of the stream of blood within the hollow fiber and to allow the one or more plasma elements of the stream of blood to pass from the hollow fiber to the receiving space of the housing. Each of the plurality of beads is configured to receive a toxin molecule from the one or more plasma elements.

Small molecules for treating breast cancer

Small molecule inhibitors of XBP1 splicing by IRE1 are provided, as well as methods for their use in treating or preventing cancer (e.g., endocrine resistant breast cancer), diabetes, and obesity.

PREDICTING DRUG-TARGET INTERACTIONS AND USES FOR DRUG REPOSITIONING AND REPURPOSING

Described herein are methods of predicting drug-target interactions and methods of using the information for drug repurposing. The methods described herein combine different descriptors, including, for example, atom pair similarity, shape, topology and chemical signatures, physico-chemical functional descriptors, contact points of the ligand and the target protein, chemical similarity, and docking score.

Vascular endothelial receptor specific inhibitors

The present application describes isoindoles and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful inhibitors of VEGFR.

Treating melanoma with mebendazole and a mitogen-activated kinase inhibitor

Provided herein are methods for treating melanoma in a subject.

Small molecule inhibitors of botulinum neurotoxins

The invention provides potent quinolinol-based BoNT/A small-molecule inhibitors of botulinum neurotoxins, in particular of Clostridium botulinum serotype A neurotoxins. The invention also provides methods of using these small-molecule inhibitors to inhibit infections by Clostridium botulinum, as well as, methods of preventing infections by Clostridium botulinum through materials that may be ingested.

SMALL MOLECULE INHIBITORS OF XBP1 SPLICING

Small molecule inhibitors of XBP1 splicing by IRE1 are provided, as well as methods for their use in treating or preventing cancer (e.g., endocrine resistant breast cancer), diabetes, and obesity.

SMALL MOLECULE INHIBITORS OF XBP1 SPLICING

Small molecule inhibitors of XBP1 splicing by IRE1α are provided, as well as methods for their use in treating or preventing cancer (e.g., endocrine resistant breast cancer), diabetes, and obesity. 169.-. (canceled)71. The compound of claim 70 , wherein R claim 70 , R claim 70 , R claim 70 , and Rare each hydrogen; Ris substituted or unsubstituted phenyl claim 70 , L is —C(═O)NH— claim 70 , and X is phenyl or pyridyl.72. The compound of claim 70 , wherein R claim 70 , R claim 70 , R claim 70 , and Rare each hydrogen; Ris unsubstituted phenyl claim 70 , L is —C(═O)NH— claim 70 , and X is unsubstituted phenyl.73. The compound of claim 70 , wherein R claim 70 , R claim 70 , R claim 70 , and Rare each hydrogen; Ris substituted phenyl claim 70 , L is —C(═O)NH— claim 70 , and X is pyridyl. This application is a continuation of U.S. application Ser. No. 14/009,969, filed on Nov. 22, 2013, which is a U.S. national stage application under 35 U.S.C §371 of PCT/US2012/032110, filed on Apr. 4, 2012, which claims the benefit of U.S. Provisional Application No. 61/471,479, filed Apr. 4, 2011. The above-listed applications are incorporated herein by reference in their entireties.This invention was made with government support under grant numbers U54-CA149147 awarded by the National Institutes of Health and BC073977 awarded by the Department of Defense. The government has certain rights in the invention.Approximately 70% of newly diagnosed breast cancer patients are estrogen receptor-α positive (ER+). However, almost 50% of all ER+ breast tumors will not respond to endocrine therapy. Tamoxifen produces an overall 26% proportional reduction in mortality but many ER+ tumors that show an initial response eventually recur. Resistance to endocrine therapy remains a significant clinical problem and advanced ER+ breast cancer is largely an incurable disease.X-Box binding protein 1 (XBP1) is a key component of the signaling mechanism that contributes to endocrine resistance in breast ...

Small molecule inhibitors of AGBL2

Small molecule inhibitors of AGBL2 are provided, as well as methods of using the inhibitors to treat or prevent cancer and neurologic disorders.

Methods for treating virus infection or proliferation

A method for treating against, or at least inhibiting or suppressing, the proliferation of an internal ribosome entry site-utilizing virus (IRES-utilizing virus) involves administering a compound, a tautomer, or a pharmaceutically acceptable salt thereof, in an amount effective for inhibiting replication of the IRES-utilizing virus in cells, wherein the compound is represented by the formula:wherein each R1 is independent of the other and represents a halogen atom selected from the group consisting of bromo, chloro, fluoro and iodo.

DRUG INHIBITOR AGAINST MIGRATION AND INVASION OF CANCER CELLS AND METHODS OF TREATING AGAINST METASTASIS OF CANCER CELLS

A method for treating against, or at least inhibiting or suppressing, the proliferation of a cancer involves administering a compound, a tautomer, or a pharmaceutically acceptable salt thereof, in an amount effective for inhibiting metastasis of cancer cells, wherein the compound is represented by the formula (1): 2. The method according to claim 1 , wherein each Ris the same.3. The method according to claim 2 , wherein at least one Rrepresents chloro.4. The method according to claim 2 , wherein each Rrepresents chloro.5. The method according to claim 1 , wherein the cancer is one in which RACK1 functions as a positive regulator for cancer cell migration and metastasis.6. The method according to claim 1 , wherein the cancer is breast cancer.7. The method according to claim 1 , wherein the cancer is gliobastoma.9. The cancer inhibitor composition according to claim 8 , wherein the RACK1 inhibitor further comprises a carrier.10. The cancer inhibitor composition according to claim 8 , wherein each Ris the same.11. The cancer inhibitor composition according to claim 8 , wherein at least one Rrepresents chloro.12. The cancer inhibitor composition according to claim 8 , wherein each Rrepresents chloro.13. Use of a therapeutically effective amount of a cancer inhibitor according to for treating against cancer metastasis. Methods pertain to treatment against cancers involving inducing functional inactivity of a protein instrumental in cancer metastasis and invasion. More particularly, methods comprise administering an inhibitor of such a protein, RACK1, in treatment against migration and invasion of cancer cells.Cancer has been identified as a leading cause of deaths worldwide. The leading cause of cancer mortality has been attributed to the migration and invasion (metastasis) of cancer cells to distant organs, but apparently not necessarily attributed to localized cancer.Long standing efforts to develop effective treatments against cancer are legion. Despite efforts to ...

METHODS FOR MODULATING PLANT RESPONSE TO ENVIRONMENTALLY-INDUCED STRESS

Compounds and methods are described herein that are effective to modulate plant response (e.g., plant susceptibility) to environmentally-induced stress. The compounds and methods described herein advantageously may be used to modulate environmental stress resistance in a wide variety of plants. Environmental stresses include, for example, high light intensity (UV exposure), temperature (e.g., high heat), high soil salinity, and low soil moisture (e.g., drought). As used herein, environmental stresses include any conditions that result in increased generation of reactive oxygen species (ROS) and accumulation of ROS in the plant cells. The compounds described herein that are effective to modulate resistance to the stress prevent, directly or indirectly, or increase phosphorylation of Tyrof the RACK1A protein. 1. A method for modulating environmental stress resistance in a plant , the method comprising applying to plant material , area of cultivation , or combination thereof an amount of a compound effective to increase Tyr248 phosphorylation of RACK1A in response to the environmental stress.2. The method of claim 1 , wherein the plant material comprises foliage claim 1 , stem claim 1 , roots claim 1 , soil claim 1 , or a combination thereof.6. The method according to claim 1 , wherein the environmental stress is selected from the group consisting of high light intensity claim 1 , high soil salinity claim 1 , low soil moisture claim 1 , and heat.7. The method according to claim 1 , wherein the compound is diluted in liquid media prior to application to the plant material or area of cultivation.8. A method for increasing resistance to environmental stress in a plant claim 1 , the method comprising applying to plant material claim 1 , area of cultivation claim 1 , or combination thereof an amount of a compound effective to decrease Tyr248 phosphorylation of RACK1A in response to the environmental stress.9. The method of claim 8 , wherein the plant material comprises ...

METHODS AND SYSTEMS FOR POPULATING AND SEARCHING A DRUG INFORMATICS DATABASE

The present invention provides a method for populating and searching a drug informatics database that includes receiving unprocessed data associated with a chemical compound from one or more data sources. The unprocessed data is parsed into a plurality of data objects based on a categorization associated with each of the data objects. Additional information, such as explanatory notes, is identified and associated with at least one of the data objects. The data objects are stored in entries within a data structure, where the data structure is searchable based on one or more of the data objects. A query for data associated with a chemical compound is received at a drug informatics database. The drug informatics database is then searched for data associated with the chemical compound and the search results are provided to a user. 1. A method for populating a drug informatics database , comprising:receiving, into a computing device, unprocessed data associated with a chemical compound from one or more data sources;parsing the unprocessed data in the computing device into a plurality of data objects based on a categorization associated with each of the data objects;identifying and associating, in the computing device, additional information including explanatory notes with at least one of the data objects; andstoring the data objects in entries within a data structure, where the data structure is searchable based on one or more of the data objects.2. The method of wherein receiving unprocessed data includes receiving data from one of chemical companies claim 1 , public databases claim 1 , and public literature.3. The method of wherein parsing the unprocessed data includes identifying one of a company name claim 1 , a company drug id claim 1 , a molecular weight claim 1 , and bibliographic information associated with a chemical compound.4. The method of wherein storing the data objects includes standardizing the data objects.5. The method of wherein standardizing the data ...

SMALL MOLECULE INHIBITORS OF BOTULINUM NEUROTOXINS

The invention provides potent quinolinol-based BoNT/A small-molecule inhibitors of botulinum neurotoxins, in particular of serotype A neurotoxins. The invention also provides methods of using these small-molecule inhibitors to inhibit infections by , as well as, methods of preventing infections by through materials that may be ingested. 2. The composition of wherein the halogen is selected from the group consisting of F claim 1 , Cl claim 1 , Br claim 1 , and I.3. The composition of wherein the aryl group is a phenyl claim 1 , biphenyl claim 1 , thiophenyl claim 1 , or indolyl ring.4. The composition of further comprising a pharmaceutically acceptable carrier claim 1 , excipient claim 1 , diluent claim 1 , or adjuvant.5. The composition of claim 1 , which further includes a pharmaceutically acceptable salt of the compound of Formula 1.7. The method of wherein the composition includes two or more compounds of Formula 1.8. The method of wherein the composition includes a pharmaceutically acceptable salt of a compound of Formula 1.9. The method of wherein the composition further comprises a pharmaceutically acceptable carrier claim 6 , excipient claim 6 , diluent claim 6 , or adjuvant.10Clostridium botulinumClostridium botulinum. The method of wherein the botulinum neurotoxin is a serotype A neurotoxin claim 6 , and inhibiting the botulinum neurotoxin inhibits or prevents a infection.11. The method of wherein the subject is an animal.12. The method of wherein the subject is a human.16Clostridium botulinumClostridium botulinum. The method of wherein the botulinum neurotoxin is a serotype A neurotoxin claim 15 , and inhibiting the botulinum neurotoxin inhibits or prevents a infection.17. The method of claim 15 , wherein the composition includes two or more compounds of Formula 2.18. The method of claim 15 , wherein the composition includes a pharmaceutically acceptable salt of a compound of Formula 2.19. The method of claim 15 , wherein the composition further comprises ...

METHODS FOR TREATING VIRAL INFECTION

A method effective in treating a viral infection involves administering a therapeutically effective amount of at least one compound capable of inhibiting expression of at least a portion of a virus genome containing an internal ribosomal entry site, or a pharmaceutically acceptable salt thereof. The compound has an azole moiety comprising a five member heterocyclic ring containing at least one nitrogen atom, a hydrophobic moiety bonded to the heterocyclic ring of the azole, and a donor/acceptor moiety bonded to the heterocyclic ring having at least one of hydrogen bond donor and a hydrogen bond acceptor. 1. A method of treating a viral infection by inhibiting expression of at least a portion of a virus genome containing an internal ribosomal entry site , said method comprising: i. an azole moiety comprising a five member heterocyclic ring containing at least one nitrogen atom;', 'ii. a hydrophobic moiety bonded to the heterocyclic ring of the azole; and', 'iii. a donor/acceptor moiety bonded to the heterocyclic ring, the donor/acceptor moiety comprising at least one of hydrogen bond donor and a hydrogen bond acceptor., 'a. administering a therapeutically effective amount of a compound to inhibits expression of at least a portion of a virus genome containing an internal ribosomal entry site, or a pharmaceutically acceptable salt thereof, said compound comprising2. The method according to claim 1 , wherein the five member heterocyclic ring of the azole moiety comprises a nitrogen at the 1 position claim 1 , a nitrogen at the 3 position claim 1 , and a nitrogen at the 4 position.3. The method according to claim 1 , wherein the compound further comprises a hydrophilic moiety bonded to the nitrogen atom of the heterocyclic ring of the azole moiety.4. The method according to claim 3 , wherein the hydrophilic moiety bonded to the nitrogen atom of the heterocyclic ring of the azole moiety comprises an amine.5. The method according to claim 3 , wherein the hydrophobic moiety ...

METHOD FOR PREDICTING DRUG-TARGET INTERACTIONS AND USES FOR DRUG REPOSITIONING

Described herein are methods of predicting drug-target interactions and method of using the information for drug repurposing. The methods described herein combine different descriptors including, for example, shape, topology and chemical signatures, physico-chemical functional descriptors, contact points of the ligand and the target protein, chemical similarity, and docking score. 1. A method for identifying protein-drug interactions , the method comprising:receiving test ligand molecular data corresponding to a test ligand that is a candidate drug;receiving protein molecular data corresponding to a protein;receiving reference ligand data corresponding to a reference ligand that binds to the protein;calculating, by a computer system, a shape score including one or more shape contributions, each shape contribution corresponding to a respective shape descriptor, wherein a respective contribution includes two parts, the first part providing a first shape score from a first respective shape function of the protein and the test ligand corresponding to the respective shape descriptor, and the second part providing a second shape score from a second respective shape function of the reference ligand and the test ligand corresponding to the respective shape descriptor;calculating, by a computer system, a similarity score including one or more similarity contributions, each similarity contribution corresponding to a respective similarity descriptor, wherein a respective similarity contribution provides a similarity score between a respective similarity function of the test ligand and the respective similarity function of the reference ligand;calculating, by a computer system, a correction score, the correction score being a difference between two sums, the first sum being of energies of contact points between the reference ligand and the protein, the second sum being of energies of contact points between the test ligand and the protein; andcalculating an interaction score, ...

Cadherin-11 inhibitors and methods of use thereof

Methods and systems for populating and searching a drug informatics database

The present invention provides a method for populating and searching a drug informatics database that includes receiving unprocessed data associated with a chemical compound from one or more data sources. The unprocessed data is parsed into a plurality of data objects based on a categorization associated with each of the data objects. Additional information, such as explanatory notes, is identified and associated with at least one of the data objects. The data objects are stored in entries within a data structure, where the data structure is searchable based on one or more of the data objects. A query for data associated with a chemical compound is received at a drug informatics database. The drug informatics database is then searched for data associated with the chemical compound and the search results are provided to a user.

Methods for modulating plant response to environmentally-induced stress

Compounds and methods are described herein that are effective to modulate plant response (e.g., plant susceptibility) to environmentally-induced stress. The compounds and methods described herein advantageously may be used to modulate environmental stress resistance in a wide variety of plants. Environmental stresses include, for example, high light intensity (UV exposure), temperature (e.g., high heat), high soil salinity, and low soil moisture (e.g., drought). As used herein, environmental stresses include any conditions that result in increased generation of reactive oxygen species (ROS) and accumulation of ROS in the plant cells. The compounds described herein that are effective to modulate resistance to the stress prevent, directly or indirectly, or increase phosphorylation of Tyr 248 of the RACK1A protein.

Methods for treating virus infection or proliferation

A method for treating against, or at least inhibiting or suppressing, the proliferation of an internal ribosome entry site-utilizing virus (IRES-utilizing virus) involves administering a compound, a tautomer, or a pharmaceutically acceptable salt thereof, in an amount effective for inhibiting replication of the IRES-utilizing virus in cells, wherein the compound is represented by the formula (I): wherein each R1 is independent of the other and represents a halogen atom selected from the group consisting of bromo, chloro, fluoro and iodo.

Specific inhibitors for vascular endothelial growth factor receptors

The application describes a composition comprising a therapeutically-effective amount of a compound selected from the group consisting of (see formula I); (see formula II); (see formula III); (see formula IV); and pharmaceutically-acceptable salts thereof for use for inhibiting angiogenesis or treating cancer in a subject having cancer.

Methods for treating viral infection

A method effective in treating a viral infection involves administering a therapeutically effective amount of at least one compound capable of inhibiting expression of at least a portion of a virus genome containing an internal ribosomal entry site, or a pharmaceutically acceptable salt thereof. The compound has an azole moiety comprising a five member heterocyclic ring containing at least one nitrogen atom, a hydrophobic moiety bonded to the heterocyclic ring of the azole, and a donor / acceptor moiety bonded to the heterocyclic ring having at least one of hydrogen bond donor and a hydrogen bond acceptor.

Methods and systems for populating and searching a drug informatics database

The present invention provides a method for populating and searching a drug informatics database that includes receiving unprocessed data associated with a chemical compound from one or more data sources. The unprocessed data is parsed into a plurality of data objects based on a categorization associated with each of the data objects. Additional information, such as explanatory notes, is identified and associated with at least one of the data objects. The data objects are stored in entries within a data structure, where the data structure is searchable based on one or more of the data objects. A query for data associated with a chemical compound is received at a drug informatics database. The drug informatics database is then searched for data associated with the chemical compound and the search results are provided to a user.

Method for predicting drug-target interactions and uses for drug repositioning

Described herein are methods of predicting drug-target interactions and method of using the information for drug repurposing. The methods described herein combine different descriptors including, for example, shape, topology and chemical signatures, physico-chemical functional descriptors, contact points of the ligand and the target protein, chemical similarity, and docking score.

Small molecule inhibitors of xbp1 splicing

Small molecule inhibitors of XBP1 splicing by IRE1 are provided, as well as methods for their use in treating or preventing cancer (e.g., endocrine resistant breast cancer), diabetes, and obesity.