PF 477736 (PF 00477736) is a potent, selective and ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, it is also a Chk2 inhibitor, with a Ki of 47 nM. PF 477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3, and Ret (IC50=8 (Ki), 10, 14, 23, 23, 25, and 39 nM, respectively). PF 477736 can enhance Gemcitabine antitumor activity in vitro and in vivo.
体外研究
PF 477736 is a poor inhibitor of CDK1 activity (Ki=9.9 μM, 20,000-fold versus Chk1).
PF 477736 (0.01-1 μM; 16 h) dose-dependently abrogates the camptothecin-induced DNA damage checkpoint in CA46 cells.
PF 477736 (10-48 h) abrogates the Gemcitabine-induced S-phase arrest and induces increase in apoptotic cell death in HT29 cells.
PF 477736 (180-540 nM; 4-48 h) enhances Gemcitabine cytotoxicity in dose- and time-dependent manner in HT29 cells.
体内研究
PF 477736 (4-60 mg/kg; i.p. for once a day or twice a day for four treatments) potentiates Gemcitabine antitumor activity in Colo205 xenografts.
PF 477736 (15 and 30 mg/kg; i.p.) induces histone H3 phosphorylation and DNA damage and increases apoptosis in vivo.
PF 477736 (4 mg/kg; i.v.) exhibits low systemic plasma clearance (11.8 mL/min/kg) and terminal half-life (2.9 h) in rats.
PF 477736 (4-40 mg/kg; i.p.) exhibits a dose dependent pharmacokinetics.
分子式
C22H25N7O2
分子量
419.48
CAS号
952021-60-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
溶解性数据
In Vitro:
DMSO : 125 mg/mL (297.99 mM; Need ultrasonic)
配制储备液
浓度溶剂体积质量
1 mg
5 mg
10 mg
1 mM
2.3839 mL
11.9195 mL
23.8390 mL
5 mM
0.4768 mL
2.3839 mL
4.7678 mL
10 mM
0.2384 mL
1.1920 mL
2.3839 mL
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂: