Abstract: 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.

Abstract: This disclosure provides novel compounds and methods for inhibiting BAX activity and BAX-mediated apoptosis, as well as compounds and methods for treating or preventing BAX-mediated disorders.

Abstract: 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.

Abstract: A pharmaceutical combination comprising a B-cell lymphoma 2 associated X protein (BAX) activating compound an anti-apoptotic protein inhibiting compound is provided. The disclosure also provides a method of treating cancer in a subject by administering a B-cell lymphoma 2 associated X protein (BAX) activating compound in combination with an anti-apoptotic protein inhibiting compound, such as a BCL-XL, BCL-2, BFL-1. BCL-w, or MCL-1 inhibiting compound.

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

Abstract: This disclosure provides compounds and pharmaceutically acceptable salts thereof of Formula I (Formula I) The variables, e.g. R1-R4, and Z are defined herein. Y is Y is (II). Certain compounds of Formula I are highly potent against resistant tumor cell el lines driven by BRAFV600E monomer melanoma cells (A375 or SK-MEL-239), p61-BRAFV600E dimer splice variant melanoma cells (SK-MEL-239-C4) and colorectal (RKO) and lung cancer (A549) cells, and at the same time display a highly desirable pharmacological profile in a mice tumor model.

Abstract: 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.

Abstract: This disclosure provides methods for inhibiting BAX activity and BAX-mediated apoptosis, as well as methods for treating or preventing BAX-mediated disorders, based, in part, on an unexpected discovery that eltrombopag (EO) can work as as a potent binder to the BAX trigger site and an effective direct BAX inhibitor.

Abstract: 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?) in subjects in need thereof.

Abstract: The disclosure provides compounds of Formula 1, and the pharmaceutically acceptable salts thereof. The variables in Formula 1, e.g. X1-X5, A1, A2, and R1-R4 are described herein. Such compounds are useful as prostaglandin transport (PGT) inhibitors. The disclosure further includes pharmaceutical compositions comprising a compound of Formula 1 or salt thereof and methods of using compounds of Formula 1 and salts thereof to treat diseases and disorders mediated, at least in part, by prostaglandin levels or cyclooxygenase activity. Such diseases and disorders include painful and inflammatory conditions.

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

Abstract: This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells).

Abstract: 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 RA, RB, RC, RD, L0, L1, L2, and L2, 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.

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

Abstract: This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells).

Abstract: Compounds and pharmaceutically acceptable salts thereof of Formula I are disclosed. The variables, e.g. R1-R9, 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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?) in subjects in need thereof.