CRT0066101 Hydrochloride

Protein kinase D (PKD) is a serine/threonine protein kinase that is activated by diacylglycerol, commonly downstream of PKC signaling. The three human PKD isoforms target a variety of proteins to alter cell proliferation, survival, invasion, and protein transport. CRT0066101 is an inhibitor of all three PKD isoforms (IC₅₀s = 1, 2.5, and 2 nM for PKD1, PKD2, and PKD3, respectively).¹ It exhibits selectivity for PKD against a panel of >90 protein kinases, including PKCα, PKBα, MEK, ERK, c-Raf, c-Src, and c-Abl.¹ It can block cell proliferation, induce apoptosis, and reduce the viability of pancreatic cancer cells both in vitro and in vivo.¹

CRT0066101 trihydrochloride is the trihydrochloride salt form of CRT0066101 (HY-15698). CRT0066101 trihydrochloride is an orally active PKD inhibitor with IC50 values of 1 nM, 2.5 nM and 2 nM for PKD1, PKD2, and PKD3, respectively. CRT0066101 trihydrochloride is also an inhibitor for PIM2 with an IC50 of ~135.7nM. CRT0066101 trihydrochloride exhibits anti-inflammatory activity in mice LPS (HY-D1056)-induced lung injury models, and has anticancer effects[1][2][3].

PKD1: 1 nM (IC₅₀); PKD3: 2 nM (IC₅₀); PKD2: 2.5 nM (IC₅₀); PIM2: 135.7 nM (IC₅₀)

1. Harikumar, K.B., Kunnumakkara, A.B., Ochi, N., et al. A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo Mol. Cancer Ther. 9(5),1136-1146(2010).