PROTAC EZH2 Degrader-44 

PROTAC EZH2 Degrader-44 (compound 60) is a highly efficient PROTAC degrader targeting the EZH2-PRC2 complex. By recruiting the CRBN E3 ligase and relying on the proteasome system, PROTAC EZH2 Degrader-44 simultaneously induces the degradation of core components EZH2, SUZ12 and EED, thereby significantly reducing the levels of H3K27me3 and CARM1. PROTAC EZH2 Degrader-44 exerts antiproliferative effects through a dual mechanism: on the one hand, it triggers mitochondrial dysfunction leading to decreased membrane potential; on the other hand, it strongly promotes apoptosis by regulating Bcl-2 family proteins (upregulating Bax, Caspase-3 and PARP, and downregulating Bcl-2). PROTAC EZH2 Degrader-44 exhibits only extremely low cytotoxicity in human normal mammary epithelial, liver and kidney cells, showing a favorable safety window. PROTAC EZH2 Degrader-44 is an ideal tool molecule for exploring the mechanisms of targeted therapy for triple-negative breast cancer^[1]. (Pink: EZH2 ligand (HY-147230); Blue: VHL ligand (HY-125845); Black: linker).

EZH2 is a histone methyltransferase and the catalytic subunit of Polycomb Repressive Complex 2 (PRC2). It plays a pivotal role in tumor epigenetics by transcriptionally repressing tumor suppressor genes. As an epigenetic enzyme that exerts core regulatory functions in tumorigenesis and development, EZH2 serves as a target for existing therapies and is also a key research focus for the next-generation protein degradation technology (PROTACs)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1193.50

C₆₅H₈₄N₁₂O₈S

3093642-25-9

CCN(C1CCOCC1)C2=CC(C3=CC=C(C=C3)CN4CCN(CC4)C(C5=CN(N=N5)CCCCCC(N[C@@H](C(C)(C)C)C(N6[C@@H](C[C@H](C6)O)C(NCC7=CC=C(C8=C(N=CS8)C)C=C7)=O)=O)=O)=O)=CC(C(NCC9=C(C=C(NC9=O)C)C)=O)=C2C

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. S Abulkhair H, et al. Therapeutic horizons in the development of PROTAC-based EZH2 inhibitors: recent achievements, comparative analysis, and future perspectives. RSC Adv. 2026;16(4):3034-3056. Published 2026 Jan 14.  [Content Brief]