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(R)-CR8

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Chemical Structure| 294646-77-8 同义名 : (R)​-​CR8;CR8, (R)-Isomer
CAS号 : 294646-77-8
货号 : A899287
分子式 : C24H29N7O
纯度 : 99%+
分子量 : 431.533
MDL号 : MFCD18785641
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(115.87 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Cyclin-dependent kinases (Cdks) are serine/threonine kinases and their catalytic activities are modulated by interactions with cyclins and Cdk inhibitors (CKIs)[1]. (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[2]. (R)-CR8 (5 mg/Kg; i. p. ) results in a significant reduction in lesion size at 28 days in histological assessment[3]. (R)-CR8 acts as a molecular glue degrader that depletes cyclin K. 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[4].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01659437 Mycobacterium Ulcerans Infecti... 展开 >>on 收起 << Phase 2 Phase 3 Active, not recruiting January 2018 Benin ... 展开 >> Pobè Treatment Center Pobè, Benin Ghana Agogo Presbyterian Hospital Agogo, Ghana Dunkwa Government Hospital Dunkwa, Ghana Nkawie-Toase Government Hospital Nkawie, Ghana Tepa Government Hosital Tepa, Ghana 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.32mL

0.46mL

0.23mL

11.59mL

2.32mL

1.16mL

23.17mL

4.63mL

2.32mL
参考文献

[1] Shuhui Lim, Philipp Kaldis. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013 Aug;140(15):3079-93.

[2]Bettayeb K, et al. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807.

[3] 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.

[4]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.