| 产品描述： | (R)-CR8 (CR8), a second-generation analog of Roscovitine, is a potent CDK1/2/5/7/9 inhibitor. (R)-CR8 inhibits CDK1/cyclin B (IC50=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM) and CK1δ/ε (0.4 μM). (R)-CR8 induces apoptosis and has neuroprotective effect. (R)-CR8 acts as a molecular glue degrader that depletes cyclin K |
| 靶点： |
Cdk1/cyclin B:0.09 μM (IC50);cdk2/cyclin A:0.072 μM (IC50);CDK2/cyclinE:0.041 μM (IC50);Cdk5/p25:0.11 μM (IC50);CDK7/cyclin H:1.1 μM (IC50);CDK9/Cyclin T:0.18 μM (IC50);CK1δ/ε:0.4 μM (IC50);Apoptosis; CDK |
| 体外研究： |
(R)-CR8 (CR8) (0.1-100 μM; 48 hours) is a potent inducer of apoptotic cell death with an IC50 of 0.49 μM for SH-SY5Y cell line. (R)-CR8 (0.25-10 μM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage. The CDK-bound form of (R)-CR8 has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation. Apoptosis Analysis Cell Line: SH-SY5Y cell line Concentration: 0.1, 1, 10, 100 μM Incubation Time: 24 hours Result: Reduced cell survival in a dose-dependent manner. |
| 体内研究： |
(R)-CR8 (5 mg/Kg; i.p.) results in a significant reduction in lesion size at 28 days in histological assessment. Animal Model: Adult (10 to 12 weeks old) male Sprague-Dawley rats (310 to 330 g)[2] Dosage: i.p. Administration: 5 mg/Kg Result: Resulted in a significant reduction in lesion size. |
| 参考文献： |
1. Bettayeb K, et al. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807. 2. Kabadi SV, et al. CR8, a novel inhibitor of CDK, limits microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. J Cereb Blood Flow Metab. 2014 Mar;34(3):502-13. 3. Słabicki M, et al. The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K [published online ahead of print, 2020 Jun 3]. Nature. 2020;10.1038/s41586-020-2374-x. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.317 ml |
11.587 ml |
23.173 ml |
| 5 mM |
0.463 ml |
2.317 ml |
4.635 ml |
| 10 mM |
0.232 ml |
1.159 ml |
2.317 ml |
| 50 mM |
0.046 ml |
0.232 ml |
0.463 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