In Vitro: JH-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 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.