JH-XI-10-02 (C09-1140-881)

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 IC 50 of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19In VitroJH-XI-10-02, a bivalent small molecule degrader, recruits the E3 ligase CRL4Cereblon to promote the ubiquitination and proteosomal degradation of CDK8. 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. JH-XI-10-02 induces degradation of CDK8 at 5 μM in WT Molt4 cells, no degradation in CRBN 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: Jurkat cells Concentration: 1 μM Incubation Time: 6 and 24 hours Result: Partial degradation of CDK8 upon treatment for 6 h at a concentration of 1 μM. Significant degradation of CDK8 after treatment for 24 h at a concentration of 1 μM. Western Blot AnalysisCell Line: WT Molt4 and CRBN Molt4 cells Concentration: 0.1, 0.5, 1, 2, 5 μM Incubation Time: 24 hours Result: Degradation of CDK8 at 5 μM in WT Molt4 cells. There were no degradation in CRBN Molt4 cells at any concentration.Form:SolidIC50& Target:CDK8 159 nM (IC 50 ) Cereblon. Specification: 0.98 Molecular Formula: C53H69N5O9 Molecular Weight: 920.14 PubChem CID: 133081965