CRT0066101 (dihydrochloride)

CRT0066101 dihydrochloride is a potent and orally active PKD inhibitor with IC₅₀ values of 1 nM, 2.5 nM and 2 nM for PKD1, PKD2, and PKD3, respectively^[1]. CRT0066101 dihydrochloride is also a potent PIM2 inhibitor with an IC₅₀ of ~135.7 nM. CRT0066101 dihydrochloride exhibits anti-inflammatory activity in mice LPS (HY-D1056)-induced lung injury models, and has anticancer effects^[1][2][3]. IC50 & Target:IC50: 1 nM (PKD1), 2.5 nM (PKD2), 2 nM (PKD3)^[1] In Vitro:CRT0066101 (5 µM; 1 h) dihydrochloride blockS both the basal and NT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells. CRT0066101 dihydrochloride abrogates NT-induced phosphorylation of Hsp27 (pS82-Hsp27), attenuates PKD1-mediated NF-κB activation, and abrogates expression of NF-κB-dependent-dependent proliferative and pro-survival proteins^[1].
CRT0066101 dihydrochloride significantly inhibits Panc-1 cell proliferation, with an IC₅₀ value of 1 µM. CRT0066101 dihydrochloride results in a 6-10 fold induction of apoptosis in Panc-1 cells. CRT0066101 dihydrochloride significantly reduces cell proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells but had a modest effect in Capan-2 cells^[1]. In Vivo:CRT0066101 dihydrochloride (80 mg/kg/day; oral gavage; once daily; for 21 days) dihydrochloride in Panc-1 orthotopic model potently blocks tumor growth in vivo^[1].
CRT0066101 dihydrochloride (10 mg/kg, i.p., every two days for 3 times) exhibits a protective effect against LPS-induced pneumonia and alleviates lung damage in C57BL/6J mice^[3].