Discovery of 3-(trifluoromethyl)-1H-pyrazole-5-carboxamide activators of the M2 isoform of pyruvate kinase (PKM2).

Basic Information

ID: ALA3102764

Journal: Bioorg Med Chem Lett

Title: Discovery of 3-(trifluoromethyl)-1H-pyrazole-5-carboxamide activators of the M2 isoform of pyruvate kinase (PKM2).

Authors: Xu Y, Liu XH, Saunders M, Pearce S, Foulks JM, Parnell KM, Clifford A, Nix RN, Bullough J, Hendrickson TF, Wright K, McCullar MV, Kanner SB, Ho KK.

Abstract: Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the optimization of a weakly active screening hit to a structurally novel series of small molecule 3-(trifluoromethyl)-1H-pyrazole-5-carboxamides as potent PKM2 activators.

CiteXplore: 24374270

DOI: 10.1016/j.bmcl.2013.12.028

Patent ID: