Protection of renal tissues from ischemia through inhibition of the proliferative kinases CDK4 and CDK6
AssigneesThe University of North Carolina at Chapel Hill, G1 Therapeutics, Inc., The Brigham and Women's Hospital, Inc.
InventorsDerek P. DiRocco, Norman E. Sharpless, Jay C. Strum, John E. Bisi, Patrick J. Roberts, Benjamin D. Humphreys, Kwok-Kin Wong
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Abstract
The presently disclosed subject matter relates to methods and compositions for protecting cells and or tissues from damage due to ischemia. In particular, the presently disclosed subject matter relates to the protective action of cyclin dependent kinase 4/6 (CDK4/6) inhibitors administered to subjects that have been exposed to, or that are at risk of, ischemia.
Claims21
A method of mitigating injury in a cell that proliferates in response to ischemia in a subject in need of treatment, the method comprising administering to the subject a pharmaceutically effective amount of a compound that inhibits cyclin dependent kinase 4 (CDK4) and cyclin dependent kinase 6 (CDK6), wherein the compound has a 50% inhibitory concentration (IC50) for CDK4 that is at least 6 times lower than the compound's IC50 for cyclin dependent kinase 2 (CDK2), wherein the cell proliferation is CDK4/6 dependent, and wherein the cell that proliferates in response to ischemia is a renal cell.
The method of 4, wherein the compound is administered to the subject between about 24 and about 48 hours after exposure of the subject to the ischemia-inducing event.
Dependencies are inferred from the claim text.