EZH2 Inhibitor

Tazemetostat (EPZ-6438) is a potent, selective and orally available EZH2 inhibitor. Tazemetostat inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 with a K_i value of 2.5 nM. Tazemetostat inhibits EZH2 with IC₅₀s of 11 and 16 nM in peptide assay and nucleosome assay, respectively. Tazemetostat inhibits rat EZH2 with an IC₅₀ of 4 nM. Tazemetostat also inhibits EZH1 with an IC₅₀ of 392 nM. Tazemetostat induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells.

GSK126 (GSK2816126A) is a potent, highly selective inhibitor of EZH2 methyltransferase with an IC₅₀ of 9.9 nM.

GSK343, a chemical probe, is a highly potent and selective EZH2 inhibitor with an IC₅₀ of 4 nM.

3-Deazaneplanocin A (DZNep) is a potent histone methyltransferase EZH2 inhibitor. 3-Deazaneplanocin A is a potent S-adenosylhomocysteine hydrolase (AHCY) inhibitor. 3-Deazaneplanocin A shows anti-orthopoxvirus activity.

3-Deazaneplanocin A hydrochloride (DZNep hydrochloride) is a potent histone methyltransferase EZH2 inhibitor. 3-Deazaneplanocin A hydrochlorideis a potent S-adenosylhomocysteine hydrolase (AHCY) inhibitor. 3-Deazaneplanocin A hydrochloride also has anti-orthopoxvirus and anti-variola activities.

YM1240 is an orally active dual EZH2/HDAC inhibitor with human EZH2 IC₅₀ 0.342 μM and human HDAC IC₅₀ 0.12 μM. YM1240 inhibits EZH2 pathway to reduce H3K27me3 levels, inhibits HDAC pathway to increase H3K9ac and H4ac levels. YM1240 suppresses proliferation, induces apoptosis, induces cell cycle arrest in lymphoma cells. YM1240 exhibits antitumor efficacy in lymphoma xenograft models. YM1240 can be used for the research of lymphoma.

UNC1999, a chemical probe, is a SAM-competitive, potent and selective inhibitor of EZH2/1 with IC₅₀s of <10 nM and 45 nM, repectively.

MS1943 is an orally active selective HyT degrader of EZH2 that effectively reduces EZH2 levels in cells. MS1943 has anticancer activity and exhibits cytotoxic effects in a variety of TNBC cells while sparing normal cells. In addition, MS1943 maintains high potency (IC₅₀=120 nM) in inhibiting EZH2 methyltransferase activity and is highly selective for EZH2. (Structure Note: RED, EZH2 ligand (HY-148458); Blue, Hyt (HY-W001578)).

MS177 is an effective and fast-acting EZH2 degrader. MS177 is a PROTAC that consists of a CRBN ligand, linker, and a potent enzymatic EZH2 inhibitor C24 (C24 IC₅₀): 12 nM). MS177 effectively depletes both canonical EZH2-PRC2 and noncanonical EZH2-cMyc complexes. MS177 induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest.

UNC6852 is a PRC2 PROTAC degrader, with a DC₅₀ value of 0.79 μM for EED (HeLa), 0.3 μM for EZH2 (HeLa), and 0.59 μM for SUZ12 (DLBCL). UNC6852 binds to the WD40 aromatic cage of EED and CRL2-VHL, inducing proteasomal degradation of EED, EZH2 and SUZ12. UNC6852 reduces the level of H₃K₂₇me₃ and exerts antiproliferative effects in cancer cells. UNC6852 can be used in studies related to diffuse large B-cell lymphoma, triple-negative breast cancer and prostate cancer.

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

Tulmimetostat (CPI-0209) is an orally active EZH1/EZH2 inhibitor that targets and inhibits the EZH2 enzyme.Tulmimetostat has antitumor activity and is used in a variety of solid tumor studies.

PROTAC EZH2 Degrader-1 (Compound 150d), a potent PROTAC EZH2 Degrader, exerts inhibitory effect on EZH2 methyltransferase activity with the IC₅₀ of 2.7 nM. EZH2 plays an important role in many tumorigenesis and development processes.

MS8847 is a PROTAC degrader and antiproliferative agent targeting EZH2 (DC₅₀=34.4 nM in EOL-1 MLL-rAML cells). MS8847 recruits the E3 ligase von Hippel-Lindau (VHL) to mediate the degradation of EZH2 via the ubiquitin-proteasome system. MS8847 induces antiproliferative effects in MLL-rearranged acute myeloid leukemia cells and inhibits the growth of triple-negative breast cancer cell lines or 3D triple-negative breast cancer models. MS8847 is applicable to research related to MLL-rearranged acute myeloid leukemia and triple-negative breast cancer.

PF-06726304 is a potent and selective EZH2 inhibitor. PF-06726304 inhibits wild-type and Y641N mutant EZH2 with K_is of 0.7 and 3.0 nM, respectively. PF-06726304 displays robust antitumor growth activity.

EPZ011989 is a potent and orally active Zeste Homolog 2 (EZH2) inhibitor with metabolic stability. EPZ011989 has inhibitory inhibition for EZH2 with a K_i value of <3 nM. EPZ011989 shows robust methyl mark inhibition and anti-tumor activity. EPZ011989 can be used for the research of various cancers. EPZ011989 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Gambogenic acid is an active ingredient that can be isolated from gamboge. Gambogenic acid acts as an effective inhibitor of EZH2, specifically and covalently binds to Cys668 within the EZH2-SET domain, and induces EZH2 ubiquitination. Gambogenic acid can be used for the research of cancer.

EPZ005687 is a potent and selective inhibitor of EZH2 with K_i of 24 nM, and has 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.

JQEZ5 is a potent and selective EZH2 lysine methyltransferase inhibitor. JQEZ5 SAM-competitively inhibits polycomb repressive complex 2 (PRC2) with an IC₅₀ of 80 nM. JQEZ5 has anti-tumor effects.

GSK503 is a potent and specific inhibitor of EZH2 methyltransferase with K_i^app values of 3 to 27 nM.