PKM2-IN-1

Description: PKM2-IN-1 is a novel and potent inhibitor of pyruvate kinase M2 (PKM2) with an IC50 of 2.95 uM. Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of the glycolytic pathway which is highly expressed in cancer cells. Cancer cells rely heavily on PKM2 for anabolic and energy requirements, and specific targeting of PKM2 therefore has potential as strategy for cancer therapy. PKM2-IN-1 displayed more potent PKM2 inhibitory activity than the reported optimal PKM2 inhibitor shikonin. PKM2-IN-1 also showed nanomolar antiproliferative activity toward a series of cancer cell lines with high expression of PKM2 including HCT116, Hela and H1299 with IC50 values ranging from 0.18 to 1.56 uM. Moreover, PKM2-IN-1 exhibited more cytotoxicity on cancer cells than normal cells. The identification of novel potent small molecule inhibitors of PKM2 not only offers candidate compounds for cancer therapy, but also provides a tool with which to evaluate the function of PKM2 in depth.

References: Eur J Med Chem. 2017 Sep 29; 138:343-352.