CDK5 Degrader

JHK-02-102-1 is a selective CDK5 degrader derived from the regorafenib kinase inhibitor scaffold. JHK-02-102-1 recruits CRL4_CRBN E3 ubiquitin ligase to induce ternary complex formation between CDK5 and CRBN, triggering ubiquitin-proteasome system-dependent degradation. JHK-02-102-1 achieves selectivity redirection from CDK6 to CDK5 via subtle PROTAC architecture modifications.

TMX-2172 is a selective bivalent cereblon-recruiting PROTAC-based dual CDK2 and CDK5 degrader with IC₅₀ values of 6.5 nM and 6.8 nM, respectively. TMX-2172 shows selectivity for CDK2 and CDK5 over other cell cycle CDKs (CDK1, CDK4, and CDK6) and transcriptional CDKs (CDK7 and CDK9). TMX-2172 inhibits CDK2/CDK5 enzymatic activity, induces their proteasomal degradation, reduces ASCL1 protein levels and half-life, induces cancer cell death, and exerts antiproliferative effects. TMX-2172 can be used for the research of ovarian cancer and small cell lung cancer.

SB1-G-187 is a multi-target kinase PROTAC degrader with activity against various kinases including GCK, YES1, IRAK1 and LYN. SB1-G-187 induces degradation of target kinases via a p97-dependent pathway, and forms ternary complexes with CRBN and specific functional kinases. SB1-G-187 can be used in tumor-related research.

TMX-2138 is a CDKs PROTAC degrader, with IC₅₀s of 8.7 nM, 10.9 nM, 7.0 nM and 25.7 nM for CDK1/cyclinB, CDK2/cyclinA, CDK5/p25 and CDK9/cyclinT1, respectively. TMX-2138 promotes ubiquitination and degradation of CDKs. TMX-2138 can be used for the research of ovarian cancer.