prc2

Tazemetostat (EPZ6438) is a histone methyltransferase EZH2 inhibitor (IC50=11 nM) that is orally active, selective, and SAM-competitive. Tazemetostat exhibits antitumor activity and may be used for the treatment of epithelioid sarcoma/follicular lymphoma.

Tazemetostat hydrobromide (E-7438 hydrobromide) is a potent and selective EZH2 inhibitor. Tazemetostat hydrobromide inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 (Ki: 2.5 nM). Tazemetostat hydrobromide also inhibits EZH1 (IC50: 392 nM).

A-395 is an antagonist of polycomb repressive complex 2 (PRC2) protein-protein interactions that potently inhibits the trimeric PRC2 complex (EZH2-EED-SUZ12, IC50: 18 nM).

UNC6852 contains an EED ligand (IC50 = 247 nM) and a von Hippel-Lindau ligand and is a selective polycomb repressive complex 2 (PRC2) degrader based on PROTAC.

EED226 is a potent, selective, and orally bioavailable embryonic ectoderm development (EED) inhibitor with an IC50 of 22 nM.

JQEZ5 is an inhibitor of EZH2 lysine methyltransferase (IC50 = 11.1 nM).

BRD9539 is an inhibitor of euchromatin histone methyltransferase 2 (EHMT2), also known as G9a, with an IC50 value of 6.3 μM

MS-177 is a PROTAC EZH2 degrader that promotes cholangiocarcinoma growth through the EZH2-mediated WNT7B/β-catenin pathway.MS-177 inhibits the growth of leukemia cells, induces apoptosis, and cell cycle arrest.MS-177 induces degradation of the classical EZH2-PRC2 and the non-classical EZH2-cMyc complexes and activates the immune-responsive genes in MM cells.

MAK683 hydrochloride embryonic ectodermal development (EED) inhibitor, also a potent PRC2 inhibitor, blocked cancer cell proliferation (IC50=1.014nM), with IC50 values of 59, 26, and 89 nM measured in EED Alphascreen, ELISA, and LC-MS assays, respectively.

ZLD1039 is a potent, orally bioavailable EZH2 (Enhancer of Zeste Homolog 2) inhibitor with high selectivity. It demonstrates strong, concentration-dependent inhibition of both wild-type and mutant (Y641F and A677G) PRC2 (Polycomb Repressive Complex 2) enzymatic activities, exhibiting IC50 values of 5.6, 15, and 4.0 nM, respectively. Additionally, ZLD1039 effectively suppresses breast tumor growth and metastasis.

SPEN-IN-1 binding suppresses histone H3K27 trimethylation and blocks initiation of X-chromosome inactivation. SPEN-IN-1 binding reduces the conformational space of RepA and displaces cognate interacting protein factors including PRC2 and SPEN.

Boc-NH-C4-acid is a PROTAC linker of the Alkyl/ether class, utilized in the synthesis of PROTAC1 for the degradation of EED, EZH2, and SUZ12 in [PRC2].

PROTAC EED degrader-1, a PROTAC targeting EED (pKD = 9.02), is an inhibitor of polycomb repressive complex 2 (PRC2) with a pIC50 of 8.17.

PROTAC EED degrader-2 is a PROTAC targeting EED (pKD of 9.27) and an inhibitor of polycomb repressive complex 2 (PRC2) with a pIC50 of 8.11.

Tazemetostat trihydrochloride is a selective and orally available inhibitor of EZH2 (IC50: 4 nM for rat EZH2). It inhibits the activity of human PRC2-containing wild-type EZH2 (Ki: 2.5 nM). It inhibits EZH2 (IC50s: 11 and 16 nM in peptide assay and nucleo

EED226-COOH, derived from EED226, serves as a ligand targeting the EED protein for PROTAC applications. It attaches to a VHL ligand through a linker, culminating in the formation of UNC6852, which specifically degrades PRC2[1].

PROTAC EZH2 Degrader-3 (compound ZJ-20) is a potent EZH2 degrader that exhibits strong inhibitory effects not only on EZH2 protein expression but also on the levels of other PRC2 subunits and H3k27me3 protein. Additionally, PROTAC EZH2 Degrader-3 demonstrates antiproliferative activity by blocking the cell cycle at the G0-G1 phase and inducing apoptosis (cell death). At a concentration of 5 μM and over a period of 24 hours, it effectively suppresses the expression of these critical proteins involved in cell regulation and growth.

MS147 is a VHL-based PROTAC PRC1 degrader. It shows binding affinity (Kd) of 3.0 μM to EED and 450 nM to VHL. The compound selectively targets the EED protein, a crucial component of PRC2, through its EED ligand portion, and interacts with PRC1 core components BMI1 and RING1B. This interaction enables MS147 to recruit BMI1 and RING1B near VHL, leading to their degradation. As a result, MS147 reduces the ubiquitination level of H2AK119ub, thereby impacting the proliferation of cancer cells.

EZH2-IN-23 (Compound 25) is an EZH2 inhibitor, exhibiting potent enzymatic inhibition against the PRC2 complex [EZH2, EED, SUZ12, AEBP2, and RbAp48] with an IC50 of 0.8 nM. It inhibits H3K27 trimethylation in cells with an IC50 of 40 nM. In rats, EZH2-IN-23 demonstrates excellent pharmacokinetic properties, achieving 100% oral bioavailability.

EED-IN-3 is an orally active inhibitor of EED. It effectively binds with EED (IC50 = 0.62 μM) to inhibit PRC2 and reduces H3K27me3 levels. EED-IN-3 selectively inhibits PC3 cells with an IC50 of 3.69 μM and significantly suppresses colony formation and migration. This compound is useful for prostate cancer research.

rel-A-395 hydrochloride is the relative configuration of A-395 hydrochloride. A-395 is an antagonist of protein-protein interactions within the polycomb repressive complex 2 (PRC2). It inhibits the trimeric PRC2 complex (EZH2-EED-SUZ12) with an IC50 value of 18 nM.

PROTACEZH2 Degrader-9 is an orally active EZH2 PROTAC degrader, operating through the ubiquitin-proteasome pathway. It effectively reduces the PRC2 core subunit and potently inhibits H3K27me3 without affecting common CRBN neo-substrates, showing selectivity towards GSPT1 and IKZF1/3. The compound exhibits strong antiproliferative effects on various cancer cell lines by inducing cell cycle arrest and apoptosis (apoptosis). Additionally, PROTACEZH2 Degrader-9 reverses PRC2-mediated gene silencing and suppresses the activation of EZH2 non-catalytic target genes. This compound is applicable in research on leukemia, lymphoma, and non-small cell lung cancer.

PROTAC EZH2Degrader-44 (compound 60) is a potent PROTAC degrader that targets the EZH2-PRC2 complex. It functions by recruiting the CRBN E3 ligase, relying on the proteasome system to degrade the core components EZH2, SUZ12, and EED, effectively reducing H3K27me3 and CARM1 levels. This compound exhibits antiproliferative effects through a dual mechanism: inducing mitochondrial dysfunction, which leads to decreased membrane potential, and regulating Bcl-2 family proteins (by upregulating Bax, Caspase-3, and PARP and downregulating Bcl-2), thereby significantly promoting apoptosis. PROTAC EZH2Degrader-44 demonstrates minimal cytotoxicity in human normal breast epithelial, liver, and kidney cells, providing a favorable safety profile. It is an ideal tool molecule for exploring targeted therapy mechanisms for triple-negative breast cancer.

PROTAC EZH2 Degrader-19 (compound 6) is a PROTAC protein degrader specifically targeting EZH2, with an IC50 of 15.00 nM. It effectively degrades all PRC2 subunits (EZH2, SUZ12, EED, RbAp48) in a concentration- and time-dependent manner. This compound demonstrates antiproliferative activity in cancer cells and is useful for cancer-related research.