Information
Riviciclib hydrochloride (P276-00) is a novelCDK1,CDK4andCDK9inhibitor withIC50of 79 nM, 63 nM and 20 nM, respectively. Riviciclib hydrochloride (P276-00) induces apoptosis. Phase 2/3.
In vitro
P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E. It shows potent antiproliferative effects against various human cancer cell lines, including HCT-116, U2OS, H-460, HL-60, HT-29, SiHa, MCF-7, Colo-205, SW-480, PC-3, Caco2, T-24 with an IC50 ranging from 300 to 800 nmol/L, and is found to be highly selective for cancer cells as compared with normal fibroblast cells. P276-00 can down-regulate cyclin D1 and Cdk4 in an ATP- competitive manner and decrease Cdk4-specific pRb Ser780 phosphorylation. P276-00 also induces apoptosis by actving cellular caspase-3 activity and DNA ladder formation.
In vivo
P276-00, administered i.p. at 50 mg/kg daily for 20 treatments can significantly induce growth inhibition of murine colon cancer (CA-51). However, in murine lung carcinoma model (Lewis lung), an increased dose of 60 mg/kg (30 mg/kg twice daily) administered every alternate day i.p. for 7 treatments shows significant inhibition in the growth. And it also inhibit the growth of human colon carcinoma HCT-116 xenograft and human non-small cell lung carcinoma H-460 xenograft. Efficacy Studies show its maximum tolerated dose is 78 mg/kg/d.
Cell Data
cell lines：
Concentrations：~5.0 μM
Incubation Time：48 h
Powder Purity:≥99%
