COMPOSITIONS, ASSAYS, AND METHODS FOR DIRECT MODULATION OF FATTY ACID METABOLISM

WIPO Patent Application WO/2018/006009

A3

This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid β-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid β-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

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WALENSKY LOREN D (US)
ESCUDERO SILVIA (US)

PCT/US2017/040360

February 08, 2018

June 30, 2017

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DANA FARBER CANCER INST INC (US)

A61K31/00; A61K31/11; A61K31/4045; A61K31/495

US20150246955A1	2015-09-03
EP1331227A1	2003-07-30

MCANDREW ET AL.: "Structural Basis for Substrate Fatty Acyl Chain Specificity CRYSTAL STRUCTURE OF HUMAN VERY-LONG-CHAIN ACYL-CoA DEHYDROGENASE", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 283, no. 14, 4 April 2008 (2008-04-04), pages 9435 - 9443, XP055263190

KOIPALLY, Joseph J. et al. (US)

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