EZH2 Degrader

PROTAC EZH2 Degrader-38 (Compound 17) is a EZH2 PROTAC degrader with an IC₅₀ of 165.00 nM. PROTAC EZH2 Degrader-38 functionally inhibits the methyltransferase activity of EZH2 and competitively binds to the SAM-binding pocket of the EZH2 SET domain.

MS8815 is a EZH2 PROTAC degrader, with a DC₅₀ of 140 nM in MDA-MB-453 triple-negative breast cancer (TNBC) cells and an IC₅₀ of 8.6 nM against human EZH2. MS8815 induces ubiquitin-proteasome system-mediated degradation of EZH2, reduces the levels of EED, SUZ12, FOXM1, H3K27me3 and global m₆A, and increases the protein level of HMGCS2. MS8815 can be used in the research of breast cancer and prostate cancer.

MS4322 (YS43-22) is a specific PRMT5 PROTAC degrader. MS4322 reduces the PRMT5 protein level with a DC₅₀ of 1.1 μM in MCF-7 cells. MS4322 inhibits the methyltransferase activity of PRMT5 with an IC₅₀ of 18 nM. MS4322 promotes ubiquitination and degradation of PRMT5. MS4322 can be used for the research of breast cancer, lung cancer, and hepatocellular cancer. (Pink: PRMT5 ligand (HY-173092); Blue: E3 ligase ligand HY-112078); Black: linker (HY-124780); E3+linker (HY-173093 )).

NUCC-0226272 is a potent PROTAC that targets EZH2 for degradation. NUCC-0226272 has anti-proliferative effect. NUCC-0226272 has the potential for cancer research.

PROTAC EZH2 Degrader-2 is a PROTAC EZH2 inhibitor. PROTAC EZH2 Degrader-2 degrades EZH2 in SU-DHL-6 cells in a dose-dependent manner. PROTAC EZH2 Degrader-2 induces apoptosis and reduces mitochondrial membrane potential in SU-DHL-6 cells. PROTAC EZH2 Degrader-2 has anti-cancer and anti-proliferative activity.

Tazemetostat de(methylene morpholine)-O-C3-O-C-COOH (Compound 21b) incorporates a ligand for EZH2, and a PROTAC linker, which recruit E3 ligases. Tazemetostat de(methylene morpholine)-O-C3-O-C-COOH (Compound 21b) can be used for the research of lymphoma.

PROTAC EZH2 Degrader-3 is a EZH2 PROTAC degrader. PROTAC EZH2 Degrader-3 induces the global degradation of the PRC2 complex (including EZH2, SUZ12, EED, RbAp48) via the ubiquitin-proteasome pathway and downregulates H3K27me3 levels. PROTAC EZH2 Degrader-3 inhibits cancer cell proliferation and induces their apoptosis. PROTAC EZH2 Degrader-3 can be used in research related to lymphoblastoma and diffuse large B-cell lymphoma.

PROTAC EZH2 Degrader-9 is orally active EZH2 PROTAC degrader degrading EZH2 via the ubiquitin-proteasome pathway. PROTAC EZH2 Degrader-9 downregulates PRC2 core subunits and potent inhibition of H3K27me3 without affecting common CRBN neosubstrates while it was selective over GSp'T1 and ikZF1/3. PROTAC EZH2 Degrader-9 exhibits potent antiproliferative activity against multiple cancer cell lines by inducing cell cycle and apoptosis. PROTAC EZH2 Degrader-9 reverses PRC2-mediated gene silencing and inhibiting EZH2 non-catalytic target gene activation. PROTAC EZH2 Degrader-9 can be used for leukemia, lymphoma, and non-small cell lung cancer research.

PROTAC EZH2 Degrader-26 (compound 11) is an EZH2 degrader developed based on PROTAC technology. PROTAC EZH2 Degrader-26 has an IC₅₀ of 5.80 nM against EZH2. PROTAC EZH2 Degrader-26 exhibits micromolar-level enzyme inhibitory activity against EZH1, with an EZH1 IC₅₀ of 0.06 μM.

PROTAC EZH2 Degrader-13 is an EZH2-targeting PROTAC with an IC₅₀ of 2.70 nM. PROTAC EZH2 Degrader-13 exerts antiproliferative effects in cancer cells. PROTAC EZH2 Degrader-13 can be used for the research of cancer.

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.

PROTAC EZH2 Degrader-21 is an EZH2 degrader developed based on PROTAC technology. PROTAC EZH2 Degrader-21 induces the degradation of the target protein EZH2 via specific recruitment of the cIAP E3 ligase. PROTAC EZH2 Degrader-21 exhibits significant inhibitory activity in a variety of lymphoma cell lines. PROTAC EZH2 Degrader-21 can be used for research on the pathogenesis of lymphoma.