Loading patent…
AssigneeDana-Farber Cancer Institute, Inc.
InventorsLoren D. Walensky, Silvia Escudero
Estimating the term…
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.
A method for inhibiting the interaction between Myeloid Cell Leukemia-1 (MCL-1) and Very Long Chain Acyl CoA Dehydrogenase (VLCAD), the method comprising contacting a mixture comprising MCL-1 and VLCAD with an agent that binds VLCAD and/or MCL-1 to disrupt VLCAD activity;
A method for treating a Myeloid Cell Leukemia-1 (MCL-1) associated disease or disorder in a human subject in need thereof, the method comprising administering to the human subject a composition comprising an agent that inhibits interaction between MCL-1 and Very Long Chain Acyl CoA Dehydrogenase (VLCAD), or directly inhibits VLCAD, thereby treating the disease or disorder in the human subject, wherein the agent comprises a stapled polypeptide, and wherein the stapled polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NOs:
A method of reducing or lowering fatty acid β-oxidation thereby decreasing ATP/energy production in a cell, the method comprising contacting the cell with a composition comprising an agent that inhibits the interaction between MCL-1 and VLCAD, or directly inhibits VLCAD, wherein the method results in reducing or lowering fatty acid β-oxidation in the cell relative to fatty acid β-oxidation in the cell not contacted with the agent, wherein the agent comprises a stapled polypeptide, and wherein the stapled polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NOs:
A method for inhibiting the interaction between MCL-1 and VLCAD, the method comprising contacting a mixture comprising MCL-1 and VLCAD with an agent that binds VLCAD and/or MCL-1 to disrupt VLCAD activity, wherein the agent comprises a stapled polypeptide, and wherein the stapled polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NOs:
Dependencies are inferred from the claim text.