US 9,808,461 B2
Protection of renal tissues from ischemia through inhibition of the proliferative kinases CDK4 and CDK6
Derek P. DiRocco, Brookline, MA (US); Norman E. Sharpless, Chapel Hill, NC (US); Jay C. Strum, Hillsborough, NC (US); John E. Bisi, Apex, NC (US); Patrick J. Roberts, Durham, NC (US); Benjamin D. Humphreys, Brookline, MA (US); and Kwok-Kin Wong, Arlington, MA (US)
Assigned to The University of North Carolina at Chapel Hill, Chapel Hill, NC (US); G1 Therapeutics, Chapel Hill, NC (US); and Brigham and Women's Hospital, Boston, MA (US)
Appl. No. 13/988,158
Filed by Derek P. DiRocco, Brookline, MA (US); Norman E. Sharpless, Chapel Hill, NC (US); Jay C. Strum, Hillsborough, NC (US); John E. Bisi, Apex, NC (US); Patrick J. Roberts, Durham, NC (US); Benjamin D. Humphreys, Brookline, MA (US); and Kwok-Kin Wong, Arlington, MA (US)
PCT Filed Nov. 17, 2011, PCT No. PCT/US2011/061202
§ 371(c)(1), (2), (4) Date Jul. 31, 2013,
PCT Pub. No. WO2012/068381, PCT Pub. Date May 24, 2012.
Claims priority of provisional application 61/458,140, filed on Nov. 17, 2010.
Prior Publication US 2013/0303543 A1, Nov. 14, 2013
Int. Cl. A61K 31/497 (2006.01); A61K 31/519 (2006.01); A61K 31/192 (2006.01); A61K 31/436 (2006.01); A61K 31/616 (2006.01); A61K 38/13 (2006.01); A61K 31/505 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 31/192 (2013.01); A61K 31/436 (2013.01); A61K 31/616 (2013.01); A61K 38/13 (2013.01); A61K 31/505 (2013.01)] 21 Claims
 
1. 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.