Abstract: A pharmaceutical composition comprising a PD-1 inhibitor and a Hsp90 inhibitor, or a tautomer, or a pharmaceutically acceptable salt thereof, wherein the Hsp90 inhibitor is 3-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(1-methyl-indol-5-yl)-5-hydroxy-[1,2,4] triazole or 5-hydroxy-4-(5-hydroxy-4-(1-methyl-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl)-2-isopropylphenyl dihydrogen phosphate. Also provided is a method for treating cancer in a subject in need thereof, using the pharmaceutical composition described herein.

Abstract: A pharmaceutical composition comprising a PD-1 inhibitor and a Hsp90 inhibitor, or a tautomer, or a pharmaceutically acceptable salt thereof, wherein the Hsp90 inhibitor is 3-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(1-methyl-indol-5-yl)-5-hydroxy-[1,2,4] triazole or 5-hydroxy-4-(5-hydroxy-4-(1-methyl-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl)-2-isopropylphenyl dihydrogen phosphate. Also provided is a method for treating cancer in a subject in need thereof, using the pharmaceutical composition described herein.

Abstract: The invention relates to certain compounds or pharmaceutically acceptable salts, solvates, clathrates, or prodrugs thereof, that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound.

Abstract: The invention relates to compounds of structural formula (I) and structural formula (VI): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein R, R1, R2, Z, L, and n are defined herein. Those compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Abstract: Methods of treating certain cancers with ganetespib or NVP-AUY922 are disclosed. Also provided are methods of treating cancer wherein the cancer has an FGFR3 mutation and/or a low level expression of UGT1A, and/or a low level expression of UGT1A9 and/or UGT1A10. Also provided are methods of treating cancer with a mutation in FGFR3 and/or a low level expression of UGT1A, and/or a low level expression of UGT1A9 and/or UGTIA10, with ganetespib or NVP-AUY922, in combination with an FGFR3 inhibitor such as BGJ398 and AZD4547.

Abstract: A pharmaceutical combination comprising a topoisomerase I inhibitor, and an Hsp90 inhibitor according to the following formulae (I) (Ia) a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables in the structural formulae are defined herein. Also provided is a method for treating a proliferative disorder in a subject in need thereof, using the pharmaceutical combination described herein.

Abstract: A pharmaceutical combination comprising a BRAF inhibitor, and an Hsp90 inhibitor according to the following formulae (I): or a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables are defined therein. Also provided is a method for treating a proliferative disorder in a subject in need thereof, using the pharmaceutical combination described herein.

Abstract: A pharmaceutical combination comprising an EGFR inhibitor and an Hsp90 inhibitor according to the following formulae (I) or (Ia) a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables in the structural formulae are defined herein. Also provided are methods for treating a proliferative disorder in a subject in need thereof using pharmaceutical combinations disclosed herein.

Abstract: The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

Abstract: The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, and prodrug thereof, wherein Ra, Rb, and R2 are defined herein. These compounds inhibit tubulin polymerization and/or target vasculature and are useful for treating proliferative disorders, such as cancer.

Abstract: The present invention is directed to a compound comprising a bis[thiohydrazide amide] or a deprotonated form thereof, complexed to a transition metal cation, wherein the bis[thiohydrazide amide] is represented by Structural Formula (I), or a prodrug, isomer, ester, salt, hydrate, solvate, polymorph or a deprotonated form thereof. In one embodiment, the compound is represented by Structural Formula (II), or a prodrug, isomer, ester, salt, hydrate, solvate or polymorph thereof. The present invention also provides a pharmaceutical composition comprising the compound of the invention and method of use thereof.

Abstract: Disclosed are compounds of formulae (I), (III), (IV), (VII), (X), (XI), (XII), (XIII) and (XIV), wherein the variables are as defined in the claims, and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Abstract: The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.

Abstract: Compounds of formula (I), pharmaceutical compositions comprising compounds of formula (I) and methods of inhibiting Hsp90 in a cell, treating or preventing a proliferation disorder in a mammal and treating cancer in a mammal comprising administering a compound of formula (I) to a patient or a cell. Variable R5 is an optionally substituted heteroaryl; an optionally substituted 6 to 14-membered aryl; a bicyclic 9-member heterocycle optionally substituted at any substitutable nitrogen or carbon atoms; or a substituent R18, defined herein. Ring A is an aryl or a heteroaryl optionally further substituted with one or more substituents in addition to R3. Substituent R3 is defined herein.

Abstract: The present invention provides methods for the pre-selection of a subject for therapeutic treatment with an Hsp90 inhibitor based on modulated levels of hypoxia in cancerous cells in the subject. In one embodiment, the invention provides methods for the pre-selection of a subject for therapeutic treatment with an Hsp90 inhibitor based on modulated levels of lactate dehydrogenase (LDH) in a cell, e.g., a cancerous cell. The invention also provides methods for treating cancer in a subject by administering an effective amount of an Hsp90 inhibitor to the subject, wherein the subject has been selected based on a modulated level of hypoxia. The invention further provides kits to practice the methods of the invention.

Abstract: The present invention relates to substituted pyrrole compounds of formula I and compositions comprising substituted tri-substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a tri-substituted’ triazole compound of the invention, or a pharmaceutical composition comprising such a compound.

Abstract: The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.