PD0166285

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PD0166285是 P-gp 的一个底物，是 WEE1 抑制剂，也可微弱抑制 Myt1，IC50 值分别为 24 和 72 nM。PD0166285 对 Chk1 的IC50 值为 3.433 μM。

PD0166285 is a potent Wee1 inhibitor and Chk1 inhibitor with activity at nanomolar concentrations. This G2 checkpoint abrogation by PD0166285 was demonstrated to kill cancer cells, there at a toxic highest dose of 0.5 muM in some cell lines for exposure periods of no longer than 6 hours. The deregulated cell cycle progression may have ultimately damaged the cancer cells. We herein report one of the mechanism by which PD0166285 leads to cell death in the B16 mouse melanoma cell line.

PD0166285 (0.5 μM) dramatically inhibits irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in seven of seven cancer cell lines.PD0166285 sensitizes radiation-induced cell killing in p53 mutant HT29 cells and in the E6-transfected, p53-null ovarian cancer cell line PA-1 but to a lesser extent in p53 wild-type PA-1 cells. PD0166285 abrogates irradiation-induced G2 arrest and significantly increases mitotic cell populations. PD0166285 acts as a radiosensitizer to sensitize cells to radiation-induced cell death with a sensitivity enhancement ratio of 1.23. Western Blot Analysis Cell Line:Human and mouse cancer cell lines (HCT116, HT29, DLD-1, HCT8, H460, HeLa, C 26).Concentration:0.5 μM.Incubation Time:4 h.Result:Inhibited Cdc2Y15 and CdcT14 phosphorylation.

Animal Model:Wild-type, Abcg2-/-, Abcb1a/b-/- and Abcb1a/b;Abcg2-/- FVB mice.Dosage:5 mg/kg.Administration:IV.Result:Cmax is about 400 ng/mL. P-gp, but not BCRP, limited the brain penetration of PD0166285.

PD0166285 | PD 0166285 | PD0166285

GPCR/G Protein

GPCR19

Wee1| Chk1| Myt1

Cancer

——

185039-89-8

512.43

C26H27Cl2N5O2

>98% (HPLC)

DMSO : 65 mg/mL 126.85 mM; H2O : < 0.1 mg/mL

CCN(CC)CCOc1ccc(Nc2nc3c(cn2)cc(c(=O)n3C)c2c(Cl)cccc2Cl)cc1

6-(2,6-dichlorophenyl)-2-((4-(2-(diethylamino)ethoxy)phenyl)amino)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one

(-20℃)

With Ice Pack

≥ 2 years