Albert Einstein College of Medicine

University of Toronto

Memorial Sloan Kettering Cancer Center

University of Manitoba

Evripidis Gavathiotis

Ana Maria Cuervo

Qisheng Xin

Bhaskar C Das

Sachdev Singh Sidhu

Jonathan R Lai

Felix Kopp

Ulrich G Steidl

Richard N Kitsis

Denis E Reyna

Ouathek Ouerfelli

Guangli Yang

James Hsieh

Emily H Cheng

Paul Jeng

Bogos Agianian

Dulguun Amgalan

Lorrie Kirshenbaum

Thomas P Garner

Emmanouil Zacharioudakis

Nikolaos Biris

Compounds and pharmaceutically acceptable salts thereof of Formula I are disclosed. The variables, e.g. R-R, X, and Y are defined herein. Certain compounds and salts of Formula I are active as CMA modulators. The disclosure provides pharmaceutical compositions containing a compound of Formula I and methods of treating disorders responsive to CMA modulation.

Benzoxazole and related compounds useful as chaperone-mediated autophagy modulators

The disclosure provides compounds of Formula I (Formula I) (c) And the pharmaceutically acceptable salts thereof. The A, B, C, and D rings and the variables, R, R, R, R, L, L, L, and L, are defined herein. Compounds and salts of Formula I are useful as inhibitors of RAF kinase dimerization, including dimerization of wild type and mutant BRAF kinases. The disclosure includes pharmaceutical compositions comprising a compound or salt of Formula I. The disclosure also includes methods of treating a cancer susceptible to treatment with an inhibitor of BRAF dimers or BRAF dimerization, comprising administering a therapeutically effective amount of a compound or salt of Formula I to a patient in need of such treatment. These cancers susceptible to treatment with an inhibitor of BRAF dimers or BRAF dimerization include melanoma, thyroid cancer, hairy cell leukemia, ovarian cancer, lung cancer, and colorectal cancer.

Compounds useful for inhibiting RAF dimers

Activators of BAX and their uses in cancer therapy are disclosed.

BAX activators and uses thereof in cancer therapy

Compounds, compositions and method of using these compounds are disclosed for treating a disease or disorder in which it is desirable to inhibit BAX, such as a cardiovascular disease or disorder.

Small molecule BAX inhibitors and uses thereof

Compounds and pharmaceutically acceptable salts thereof of Formula I are disclosed. Certain compounds and salts of Formula I are active as CMA modulators. The disclosure provides pharmaceutical compositions containing a compound of Formula I.

Compounds useful as chaperone-mediated autophagy modulators

Activators of mitofusins and their uses in treatment of diseases and disorders are disclosed.

Mitofusin activators and uses thereof

Methods are provided for identifying an agent that directly modulates a Bcl-2-associated x-protein (BAX) by promoting or disrupting dimerization of the BAX. Agents that directly modulate BAX by affecting dimerization are also provided.

Targeting dimerization of BAX to modulate BAX activity

Compounds, compositions and methods are provided for selectively activating chaperone-mediated autophagy (CMA), protecting cells from oxidative stress, proteotoxicity and lipotoxicity, and/or antagonizing activity of retinoic acid receptor alpha (RAR&#x3b1;) in subjects in need thereof.

Retinoic acid receptor antagonists as chaperone-mediated autophagy modulators and uses thereof

Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.

Synthetic antibodies to BAX and uses thereof

Described herein are phenylsulfonamido-benzofuran derivatives, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, methods, uses, and kits involving compounds of Formulae (I), (II), (III), (IV), (V), or (VI) for treating and/or preventing proliferative diseases (e.g. cancers, inflammatory diseases, and autoimmune diseases) in a subject. The compounds and pharmaceutical compositions as described herein inhibit at least one protein of the BCL-2 family in a biological sample or subject to treat and/or prevent a proliferative disease. In certain embodiments, compounds described herein are selective inhibitors of MCL-1, a BCL-2 family member protein. 

Growing community of inventors

Flushing, NY, United States of America

Evripidis Gavathiotis