CID-2011756 is a cell-active ATP competitive and specific PKD1 inhibitor that inhibits phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells.
Protein kinase D (PKD) is a novel family of serine/threonine kinases regulated by diacylglycerol, which is involved in multiple cellular processes and various pathological conditions[2]. CID 2011756 is an ATP competitive PKD inhibitor, with an IC50 of 3.2 µM for PKD1 in cell free assay, and also shows cellular pan-PKD inhibitory activity against PKD2 and PKD3 (IC50, 0.6 and 0.7 µM, respectively)[2]. Confirmed in vitro PKD1 inhibitors are then evaluated for their ability to inhibit the phosphorylation of endogenously expressed PKD1 ser916, an indicator of cellular PKD1 kinase activity. Results shows that CID 2011756 inhibites the phosphorylation of Ser916-PKD1 at levels greater than 50%. CID 2011756 is the most potent of the inhibitors with a cellular EC50 of 10 ± 0.7 µM (n = 3). Moreover, we counter screened 2011756 in IMAP-based CDK7, AKT and PLK1 assays, and find no kinase inhibition at concentrations up to 50 µM[2]. Moreover, preliminary in vitro data suggests that our most potent cell active PKD1 inhibitor, CID 2011756, has pan-PKD inhibitory effects (pKD2 IC50 = 0.6 ± 0.1; pKD3 IC50 = 0.7 ± 0.2 µM) with similar, albeit not identical, potencies which may be expected for an ATP competitive inhibitor[2].
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