CDK7 Degrader

BSJ-5-63 is a potent CDK12, CDK7, CDK9 PROTAC degrader. BSJ-5-63 BSJ-5-63 decreases the protein expression of CDK12, CDK7, CDK9, RNAPII, Cyclin K. BSJ-5-63 decreases the mRNA expression of BRCA1, BRCA2. BSJ-5-63 shows anticancer activity and has the potential for the research of prostate cancer.

CDK7 ligand 2 (Compound A6) is a CDK7 ligand. CDK7 ligand 2 can be used in the synthesis of PROTACs.

(S)-JWZ-5-13 (compound 17-Neg), a PROTAC CDK7 degrader, is a negative control compound of JWZ-5-13 (HY-161828). (S)-JWZ-5-13 displays similar in vitro CDK7 inhibition (IC₅₀ = 21.1 nM) to JWZ-5-13, but fails to induce CDK7 degradation in cells.

TMX-2138 is a CDK PROTAC degrader, with IC₅₀ values against different targets as follows: CDK1 (IC₅₀ = 8.7 nM), CDK2 (IC₅₀ = 10.9 nM), CDK5 (IC₅₀ = 7.0 nM), CDK4 (IC₅₀ = 901.0 nM), CDK6 (IC₅₀ = 465.0 nM), CDK7 (IC₅₀ = 286.0 nM), and CDK9 (IC₅₀ = 25.7 nM). TMX-2138 promotes the ubiquitination of CDK and induces its degradation via the proteasomal pathway. TMX-2138 can be used in ovarian cancer research.

CDK7 ligand 3 is a target protein ligand for CXJ2080 (HY-183070), which be used for the research of acute leukemia.

CXJ2080 is a selective PROTAC-based CDK7 degrader with a DC₅₀ of 0.88 nM. CXJ2080 recruits VHL E3 ligase to induce ubiquitin-proteasome-dependent CDK7 degradation, disrupts the CDK7-cyclin H-MAT1 complex, suppresses CDK7-dependent phosphorylation of RNA polymerase II CTD Ser5, CDK1 Thr161, and CDK2 Thr160. CXJ2080 activates the p53-p21 axis, suppresses MYC-driven signaling, induces leukemia cell cycle arrest, apoptosis, and differentiation, reduces CD117 expression, spares platelets and normal PBMCs, maintains sustained CDK7 degradation post-washout. CXJ2080 can be used for the research of acute leukemia.