SMI-4a

SMI-4a is a potent and selective small molecule inhibitor of Pim kinases, particularly Pim1 (IC50 ~17–21 nM), with modest activity against Pim2 and little to no significant inhibition of other serine/threonine or tyrosine kinases[2][7]. It acts as an ATP-competitive inhibitor. Mechanistically, SMI-4a induces G1 phase cell cycle arrest and apoptosis via the mitochondrial pathway in cancer cells. It downregulates c-myc expression and upregulates p27Kip1. Additionally, it inhibits PRAS40 phosphorylation and mTORC1 activity by activating AMPK[2][5]. Preclinical studies have shown that SMI-4a suppresses the growth of various cancer cell lines—including leukemia, lymphoma, prostate cancer—and has demonstrated efficacy in animal xenograft models[8][5]. Recent research also suggests its potential for treating osteoarthritis by inhibiting PIM1-mediated NLRP3 inflammasome activation in macrophages[6].

Other names

5-[[3-(trifluoromethyl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione