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AssigneeDana-Farber Cancer Institute, Inc.
InventorsLoren D. Walensky, Silvia Escudero
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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.
An MCL-1 Stabilized Alpha-Helix of BCL-2 domain (SAHB) peptide comprising an amino acid sequence that is identical to the amino acid sequence set forth in any one of SEQ ID NOs:
An MCL-1 Stabilized Alpha-Helix of BCL-2 domain (SAHB) peptide comprising the amino acid sequence set forth in any one of SEQ ID NOs:
A photoreactive SAHB (pSAHB) comprising (a) an amino acid sequence set forth in any one of SEQ ID NOs:61-63;
An MCL-1 Stabilized Alpha-Helix of BCL-2 domain (SAHB) peptide comprising the amino acid sequence set forth in any one of SEQ ID NOs:
Dependencies are inferred from the claim text.