Biological Activity of TCS PIM-1 1

TCS PIM-1 1(sc-204330) is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM).
IC50 value: 50 nM [1]
Target: Pim-1
TCS PIM-1 1 bound convincingly within the ATP-binding site of Pim-1 suggesting an ATP-competitive inhibitory mechanism. Preliminary data further suggested that 1 lacked in vitro inhibitory activity toward related serine/threonine kinases Pim-2 and MEK1/2 (IC50 > 20 lM). Hence, small molecules similar to TCS PIM-1 1 may serve as useful starting scaffolds for the development of other improved yet selective Pim-1 inhibitors.

References on TCS PIM-1 1

[1]. Cheney IW, et al. Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1679-83.
Abstract
A novel series of highly potent substituted pyridone Pim-1 kinase inhibitors is described. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with the most potent Pim-1 inhibitor reported (IC(50)=50 nM). A hydrogen bond matrix involving the Pim-1 inhibitor, two water molecules, and the catalytic core, together with a potential weak hydrogen bond between an aromatic hydrogen on the R(1) phenyl ring and a main-chain carbonyl of Pim-1, accounts for the overall potency of this inhibitor.