CRT0066101 is a potent, orally active PKD inhibitor with IC 50 values of 1 nM, 2.5 nM, and 2 nM for PKD1, PKD2, and PKD3, respectively [1]. Additionally, it inhibits PIM2 with an IC 50 of approximately 135.7 nM and demonstrates anticancer effects [2].

PKD1:1 nM, PKD2:2.5 nM, PKD3:2 nM

CRT0066101, at a concentration of 5 µM for 1 hour, blocks both the basal and NT-induced activation of pS916-PKD1/2 in Panc-1 and Panc-28 cells. It inhibits NT-induced phosphorylation of Hsp27 (pS82-Hsp27), reduces PKD1-mediated activation of NF-κB, and suppresses the expression of NF-κB-dependent proliferation and survival proteins [1]. CRT0066101 significantly inhibits Panc-1 cell proliferation, with an IC50 of 1 µM, and induces apoptosis in Panc-1 cells by 6-10 times. It notably decreases the proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells, while exerting some effect on Capan-2 cells [1].

CRT0066101 (80 mg/kg/day; oral gavage; once daily; for 21 days) effectively inhibits tumor growth in vivo in the Panc-1 orthotopic model. [1] Animal Model: CR-UK nu/nu mice injected with Panc-1 cells [1] Dosage: 80 mg/kg/day Administration: Oral gavage; once daily; for 21 days Result: Potently blocked tumor growth in vivo.