||10 mM in DMSO
||Powder -20oC 3 years 4oC 2 years In solvent -80oC 6 months -20oC 1 month
(Z)-SMI-4a is a selective ATP-competitive Pim-1 kinase inhibitor with an IC50 of 21 nM for Pim-1 compared to an IC50 of 100 nM for Pim-2 and with little or no activity against a panel of 50 other kinases tested. IC50 value: 21 nM (Pim1); 100 nM (Pim2)  Target: Pim-1
How to use:
in vitro: Incubation of pre-T-LBL cells with (Z)-SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with (Z)-SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of (Z)-SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells . Ectopic expression of phosphomimetic mutants of eIF4B conferred resistance to apoptosis by the Pim kinase inhibitor (Z)-SMI-4a in Abl-transformed cells .
in vivo: In immunodeficient mice carrying subcutaneous pre-T-LBL tumors, treatment twice daily with (Z)-SMI-4a caused a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries .
. Lin YW, et al. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010 ;115(4):824-33.
. Yang J, et al. eIF4B phosphorylation by pim kinases plays a critical role in cellular transformation by Abl oncogenes. Cancer Res. 2013 Aug 1;73(15):4898-908.