|Solubility||Soluble in DMSO.|
|Declaration||Manufactured by SynKinase.|
|Other Product Data||
Target: Chk1 | Kinase Group: CAMK | Substrate: Serine-Threonine
Click here for Original Manufacturer Product Datasheet
Our product description may differ slightly from the original manufacturers product datasheet.
|Shipping and Handling|
|Short Term Storage||+4°C|
|Long Term Storage||-20°C|
|Use/Stability||Stable for at least 2 years after receipt when stored at -20°C.|
|Product Specification Sheet|
Antagonizing the Chk1-mediated cell cycle checkpoints has emerged as an attractive target for anticancer therapy. If Chk1 activity is blocked, DNA-damaged or spindle-disrupted cells would exit cell cycle arrest before full repair and subsequently undergo mitotic catastrophe or cell death. Chk1 inhibitors consequently increase the therapeutic index of DNA-damaging or antimitotic agents as well. PF-0477736 is a selective, potent ATP-competitive Chk1 inhibitor, derived from PF-0394691, inhibits Chk1 (Ki, 0.49nM) and Chk2 (Ki, 47nM) in vitro. In tests, PF-0477736 was identified as a potent, selective ATP-competitive small-molecule inhibitor that inhibits Chk1 with a Ki of 0.49nM. PF-0477736 abrogates cell cycle arrest induced by DNA damage and enhances cytotoxicity of clinically important chemotherapeutic agents, including gemcitabine and carboplatin. In xenografts, PF-0477736 enhanced the antitumor activity of gemcitabine in a dose-dependent manner. PF-0477736 combinations were well tolerated with no exacerbation of side effects commonly associated with cytotoxic agents.
- Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1: A. Blasina, et al.; Mol. Cancer Ther. 7, 2394 (2008)
- DNA damage detection and repair pathways-recent advances with inhibitors of checkpoint kinases in cancer therapy: S. Ashwell & S. Zabludoff; Clin. Cancer Res. 14, 4032 (2008)
- PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates docetaxel-induced efficacy in xenografts: C. Zhang, et al.; Clin. Cancer Res. 15, 4630 (2009)