Fred Hutchinson Cancer Center

University of Washington

Oricula Therapeutics LLC

Fred Hutchinson Cancer Research Center

Julian Simon

Edwin W Rubel

David W Raible

Graham Johnson

Peter C Meltzer

Qin Jiang

Xinchao Chen

R Jason Herr

Mario D Gonzalez

Weishi Miao

Sarwat Chowdhury

Kelly N Owens

Stephen H Friend

Felipe Santos

John Lamb

David Hockenbery

Heather Dunstan

Shie-Pon Tzung

David M Hockenberry

Daniel E Gottschling

Antonio Bedalov

Henry C Ou

Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Compounds and methods for preventing or treating sensory hair cell death

Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing, treating, and/or protecting against sensory hair cell death. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Compounds and methods for preventing, treating and/or protecting against sensory hair cell death

Compounds are described that are useful for treating an apoptosis-associated disease, which are specifically cytotoxic to tumor cells that are overexpressing Bcl-x, and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-x. Also described is a method for treating an apoptosis-associated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an active compound that is specifically cytotoxic to tumor cells that are overexpressing Bcl-x, and are much less cytotoxic in isogenic cells that are not overexpressing Bcl-x. Several scaffolds of active compounds are described.

Gain-of-function Bcl-2 inhibitors

The present invention provides methods of identifying compounds that protect against ototoxicity induced by one or more noxious stimuli, and methods of treating an individual with compounds identified using the present screening methods. Also provided are compounds demonstrated to have otoprotective effects.

Compounds that protect against sensory hair cell death

A method for identifying a compound that inhibits the NAD-dependent deacetylase activity of a SIR2 protein is disclosed. These compounds are useful for the treatment of cancers and other diseases, through the activation of silenced genes, through the promotion of apoptosis in cancerous cells, and through the inhibition of transcriptional repressor activity in oncogenes.

Methods for inhibiting deacetylase activity

The present invention provides agents and compositions for modulating the apoptotic state of a cell. The agents comprise derivatives of antimycins which bind to an anti-apoptotic Bcl-2 family member protein. Further, the agents preferentially induce apoptosis in cells that over-express anti-apoptotic Bcl-2 family member proteins and typically exhibit reduced binding affinity for cytochrome B. Pharmaceutical uses of the agents and compositions include treating apoptosis-associated disease, such as neoplasia and drug resistance, are also disclosed.

Compositions and methods for modulating apoptosis in cells over-expressing Bcl-2 family member proteins

Methods for the treatment of a proliferative disorder are provided in which a subject in need of such treatment is administered an effective amount of a compound selected from: compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein Xand Xare independently H, Cl, F, Br, I, CN, CFor NO, and Aris a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and compounds of formula (II) wherein Xand Xare each independently H, Cl, F, Br, I, CN, CFor NO; Y is (C&#x2013;C)alkylene or (C&#x2013;C)heteroalkylene; and Z is Cl, F, Br, I, CN, CFor NO.

Topoisomerase poisons for the treatment of proliferative disorders

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Seattle, WA, United States of America

Julian Simon