SMI-16a

SMI-16a is a selective Pim kinase inhibitor with IC₅₀ values of 0.15, 0.02 and 48 μM for Pim1, Pim2 and PC3 cells, respectively. IC50 & Target: IC50: 0.15 μM (Pim1), 0.02 μM (Pim2), 48 μM (PC3 cells)^[1] In Vitro: SMI-16a has excellent potency for inhibition of both Pim-1 and Pim-2^[1]. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restores osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiates BMP-2-mediated anabolic signaling while suppressing TGF-β signaling^[2]. In Vivo: Mice tolerate intraperitoneal dose of SMI-16a is 50 mg/kg daily for 5 days, while 100 mg/kg is overtly toxic. Treatment of the animals with SMI-16a for 5 days per week reduces the growth of tumors by approximately 50% and does not cause a loss of body weight. Subchronic dosing with SMI-16a does not affect the levels of red, white blood cells, including lymphocytes, monocytes, and granulocytes, indicating that the compound does not have myelosuppressive effects. SMI-16a does not have toxicity toward the liver as the albumin, alkaline phosphatase, and alanine aminotransferase levels are unchanged ^[1]. SMI-16a effectively prevents bone destruction while suppressing MM tumor growth in MM animal models^[2].