Cayman SMI-4a

The serine/threonine Pim kinases have been suggested to promote the activity of the rapamycin-sensitive mammalian target of rapamycin (mTORC1), which regulates cell growth and survival.¹ Pim kinases are overexpressed in solid cancers and hematologic malignancies, and as such have become targets of small molecule inhibitors to prevent the progression of various cancers. SIM-4a is a Pim kinase inhibitor that blocks mTORC1 activity via activation of AMPK.¹ SIM-4a kills a wide range of both myeloid and lymphoid cell lines (with IC₅₀ values ranging from 0.8 to 40 μM).² Incubation of precursor T-cell lymphoblastic leukemia/lymphoma cells with 10 μM SMI-4a induces g₁ phase cell-cycle arrest, dose-dependent induction of p27Kip1, apoptosis through the mitochondrial pathway, and inhibition of the mTORC1 pathway.² In immunodeficient mice carrying subcutaneous pre–T-LBL tumors, treatment twice daily with 60 mg/kg SMI-4a causes a significant delay in the tumor growth.²

WARNING This product is not for human or veterinary use.