Potent inhibitor of PIM-1 with IC50 values of 0.04±0.03 µM. The inhibition of PC3 prostate carcinoma cells proliferation by 21a is 49±8 µM.
Potent inhibitor of PIM-2 with IC50 values of 0.2±0.1 µM. The inhibition of PC3 prostate carcinoma cells proliferation is 49±8 µM.
OTAVAchemicals Catalogue Number: 0123300047
CAS Registry Number: N/A
Ref.: Xia et al. Synthesis and Evaluation of Novel Inhibitors of Pim-1 and Pim-2 Protein Kinases. J. Med. Chem. (2009), 52, 74–86.
Abstract: The Pim protein kinases are frequently overexpressed in prostate cancer and certain forms of leukemia and lymphoma. 5-(3-Triﬂuoromethylbenzylidene)thiazolidine-2,4-dione (4a) was identiﬁed by screening to be a Pim-1 inhibitor and was found to attenuate the autophosphorylation of tagged Pim-1 in intact cells. Although 4a is a competitive inhibitor with respect to ATP, a screen of approximately 50 diverse protein kinases demonstrated that it has high selectivity for Pim kinases. Computational docking of 4a to Pim-1 provided a model for lead optimization, and a series of substituted thiazolidine-2,4-dione congeners was synthesized. The most potent new compounds exhibited IC50s of 13 nM for Pim-1 and 2.3 µM for Pim-2. Additional compounds in the series demonstrated selectivities of more than 2500-fold and 400-fold for Pim-1 or Pim-2, respectively, while other congeners were essentially equally potent toward the two isozymes. Overall, these compounds are new Pim kinase inhibitors that may provide leads to novel anticancer agents.