SGI-1776 is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM, 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin.

The Pim family proteins are serine/threonine kinases involved in cancer progression.SGI-1776 is a potent inhibitor of all three human Pim kinases (IC50s = 7, 363, and 69 nM for Pim-1, Pim-2, and Pim-3, respectively).While it also inhibits Flt3 and haspin (IC50s = 44 and 34 nM, respectively), SGI-1776 has little effect on several other kinases, including cell cycle kinases.SGI-1776 induces apoptosis in lymphocytes from patients with chronic or acute lymphocytic leukemia but not in those from healthy donors.At 10 µM, it reduces STAT3 phosphorylation without reducing STAT3 expression in cancer cells, and this correlates with inhibition of cell proliferation.SGI-1776 also enhances the activity of sunitinib against renal cell carcinoma and resensitizes chemoresistant prostate cancer cells to taxanes.