SMI-16a, the PIM1/2 Kinase inhibitor VI, controls the biological activity of PIM1/2. This small molecular inhibitor is primarily used for Phosphorylation & Dephosphorylation applications
Pim (provirus integration site for Moloney murine leukemia virus) family proteins are highly conserved serine/threonine kinases implicated in transcription, translation, cell cycle, survival, and drug resistance through the numerous targets. SMI-16a is a potent Pim kinase inhibitor with IC50 values of 0.15nM, 0.02nM and 48nM for Pim-1, Pim-2 and Pim-3 (measured by enzymatic activity), respectively[1]. Treatment with 5μM SMI-16a for 72h showed various degree of growth inhibition (10-40%) of PC3, DU145, LNCaP, U937, K562 and MV4;11 cells cultured in media containing 10% FBS. Because SMI-4a showed to be serum-bound, it was found that DU145 cells became considerably more sensitive under serum-free conditions. The translocation of p27Kip1 to the nucleus and reduced Cdk2 activity (shown by decreased p-H1) can also observed in K562 cells cultured in RPMI containing 10% FCS after treatment with SMI-16a[2]. Intraperitoneal injection of 50mg/kg of SMI-16a five days per week reduced tumor growth of female Balb/C mice injected subcutaneously with JC cells[1].
作用机制
SMI-16a can compete with respect to ATP, suggesting that it may bind within the ATP-binding pocket of the kinase.[2]
搜索
