In vitro activity: CID-2011756, discovered from a high throughput screening campaign, is a potent, cell-active, ATP competitive and specific inhibitor of PKD (protein kinase D) with IC50 values of 0.6, 0.7 and 3.2 μM for PKD2, PKD3 and PKD1 respectively. It inhibits phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells in a concentration-dependent manner. PKD is a novel family of serine/threonine kinases regulated by diacylglycerol, which is involved in multiple cellular processes and various pathological conditions. The limited number of cell-active, selective inhibitors has historically restricted biochemical and pharmacological studies of PKD.

Kinase Assay: CID 2011756 has pan-PKD inhibitory effects (PKD2 IC50 = 0.6±0.1 uM; PKD3 IC50 = 0.7±0.2 uM) with similar, albeit not identical, potencies which may be expected for an ATP competitive inhibitor. CID 2011756 was the most potent of the inhibitors with a cellular EC50 of 10±0.7 uM (n = 3), an EC50 value comparable to that of our previously described benzoxoloazepinolone.

Cell Assay: It inhibits phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells in a concentration-dependent manner.