In vitro activity: TCS PIM-1 1, also known as sc-204330, is a highly potent substituted pyridone and selective ATP-competitive inhibitor of Pim-1 kinase with IC50 of 50 nM, it displays good selectivity over Pim-2 and MEK1/MEK2(IC50s>20,000 nM). TCS PIM-1 1 bound convincingly within the ATP-binding site of Pim-1 suggesting an ATP-competitive inhibitory mechanism. Pim-1 kinase has been implicated in inflammatory bowel disease (IBD). Therefore, Pim-1 inhibitor (PIM-Inh) such as TCS PIM-1 1 has potential for the treatment of IBD. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with TCS PIM-1 1. 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.

Kinase Assay: TCS PIM-1 1, also known as sc-204330, is a highly potent substituted pyridone and selective ATP-competitive inhibitor of Pim-1 kinase with IC50 of 50 nM, it displays good selectivity over Pim-2 and MEK1/MEK2(IC50s>20,000 nM).

Cell Assay: Pim-1 kinase inhibitor could attenuate IBD by promoting T-cell differentiation into Foxp3+ regulatory T-cells and is a promising agent for IBD therapy.