JH-XI-10-02 是由Cereblon配体和CDK配体相连的PROTAC，是一种高效的选择性 PROTAC CDK8 降解剂，IC50 值为 159 nM。JH-XI-10-02 降解 CDK8 蛋白，但对其 mRNA 水平没有影响。JH-XI-10-02 对 CDK19 无作用。
货号:ajcx39644
CAS:2209085-22-1
分子式:C53H69N5O9
分子量：920.14
溶解度:DMSO : 100 mg/mL (108.68 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

JH-XI-10-02 is a PROTAC connected by ligands for Cereblon and CDK. JH-XI-10-02 is a highly potent and selective PROTAC CDK8 degrader, with an IC50 of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19[1].

JH-XI-10-02, a bivalent small molecule degrader, recruits the E3 ligase CRL4Cereblon to promote the ubiquitination and proteosomal degradation of CDK8[1]. JH-XI-10-02 (1 μM) induces partial degradation of CDK8 in Jurkat cells upon treatment for 6 h. JH-XI-10-02 (1 μM) induces significant degradation of CDK8 after treatment for 24 h[1]. JH-XI-10-02 induces degradation of CDK8 at 5 μM in WT Molt4 cells, no degradation in CRBN null Molt4 cells at any concentration (0.1-5 μM) in WT Molt4 cells and Molt4 cells where CRBN had been subject to CRISPER/CAS9-mediated deletion for 24 h[1].

[1]. Hatcher JM, et al. Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8. ACS Med Chem Lett. 2018 Mar 18;9(6):540-545.

Protocol:

CDK8 159nM(IC50)

Cereblon