| 产品描述： | SCH900776 (S-isomer) is an effective, specific and orally bioavailable inhibitor of checkpoint kinase Chk1 (IC50: 3 nM). It also inhibitors Chk2 (IC50: 1500 nM) and cyclin-dependent kinase CDK2 (IC50: 160 nM) |
| 靶点： |
Chk;CDK |
| 体外研究： |
SCH 900776 does not significantly inhibit HLMs CYP450 isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. SCH 900776 induces a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double-stranded DNA breaks. SCH 900776 also dose-dependently suppresses accumulation of the Chk1 pS296 autophosphorylation. |
| 体内研究： |
After pretreatment 30 minutes with gemcitabine, SCH 900776 (4 mg/kg) is sufficient to induce the γ-H2AX biomarker while 8 mg/kg leads to enhanced tumor pharmacodynamic and regression responses relative to gemcitabine or SCH 900776 alone. SCH 900776 (16/32 mg/kg) dose-dependently induces improvements in tumor response. Doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity of gemcitabine on hematological parameters in BALB/c mice. |
| 参考文献： |
1. Montano R, et al. Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites. Mol Y Ther. 2012 Feb;11(2):427-38. 2. Guzi TJ, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Y Ther, 2011, 10(4), 591-602. 3. Thompson R, et al. The Mre11 nuclease is critical for the sensitivity of cells to Chk1 inhibition. PLoS One. 2012;7(8):e44021. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.658 ml |
13.289 ml |
26.578 ml |
| 5 mM |
0.532 ml |
2.658 ml |
5.316 ml |
| 10 mM |
0.266 ml |
1.329 ml |
2.658 ml |
| 50 mM |
0.053 ml |
0.266 ml |
0.532 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京