 COA |
MSDS |
 HPLC |
NMR |
| CAS No: | 920113-03-7 |
| Molecular formula(MF) | C21H20ClNO5.HCl |
| Molecular Weight(MW): | 438.3 |
| Alias |
| In vitro | DMSO | 88 mg/mL (200.77 mM) |
|---|---|---|
| Water | 88 mg/mL (200.77 mM) | |
| Ethanol | 7 mg/mL (15.97 mM) | |
| In vivo | 30% propylene glycol, 5% Tween 80, 65% D5W | 30 mg/mL |
| Description | P276-00 is a novel CDK1, CDK4 and CDK9 inhibitor with IC50 of 79 nM, 63 nM and 20 nM, respectively. Phase 2/3. | |||||||||||
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| Targets |
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| In vitro |
P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E[1]. 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[1]. 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[1]. |
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| 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[2]. And it also inhibit the growth of human colon carcinoma HCT-116 xenograft and human non-small cell lung carcinoma H-460 xenograft[2]. Efficacy Studies show its maximum tolerated dose is 78 mg/kg/d[2]. |