Histone Methyltransferase

Signaling Pathway Map

Research Area

Inhibitory Selectivity

Histone Methyltransferase Products

All (54) Histone Methyltransferase Inhibitors (50) Histone Methyltransferase Antagonists (3)

Catalog No.	Information	Product Use Citations	Product Validations
S7062	Pinometostat (EPZ5676) Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with K_i of 80 pM in a cell-free assay, demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor. Phase 1.	Nat Cell Biol, 2020, 11 Mol Brain, 2020, 29;13(1):85 Biosci Rep, 2020, 31;40(1):BSR20193515	Treatment of c-Kit+ bone marrow (BM) cells from Setd2^f/f/Vav1-Cre mice with JQ1 500nM, EPZ-5676 1uM, BAY 1143572 400 nM for 24 h. Then cells were collected to determine the proteins levels of RNA pol II (Ser2P), pol II (Ser5P), Gata1, Gata3, Myc, and β-actin by immunoblotting.
S7004	EPZ005687 EPZ005687 is a potent and selective inhibitor of EZH2 with K_i of 24 nM in a cell-free assay, 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.	Nat Commun, 2020, 11(1):604 Gastric Cancer, 2020, 10.1007/s10120-020-01094-0 Theranostics, 2020, 10(19):8494-8512	Western blot analysis of day 7 lysates from LX92 lysates treated with various EZH2 inhibitors.
S7164	GSK343 GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. GSK343 induces autophagy.	Nat Commun, 2020, 11(1):3018 Gastric Cancer, 2020, 10.1007/s10120-020-01094-0 Am J Cancer Res, 2020, 1;10(4):1194-1206 eCollection 2020	Representative confocal microscopy images of oocytes with DZNep or GSK343 treatment. The oocytes presented with a typical barrel-shaped spindle and well-aligned chromosomes on the metaphase plate not only in DZNep or GSK343 treated group but also in the control group. Spindle was recognized by α-tubulin (green) and DNA was recognized by PI (Propidium iodide, red). Scale bar = 4 μm.
S8006	BIX 01294 BIX01294 is an inhibitor of G9a histone methyltransferase with IC50 of 2.7 μM in a cell-free assay, reduces H3K9me2 of bulk histones, also weakly inhibits GLP (primarily H3K9me3), no significant activity observed at other histone methyltransferases. BIX01294 induces autophagy.	Nat Commun, 2020, 11(1):604 Oxid Med Cell Longev, 2020, 12;2020:6983268 Sci Rep, 2020, 10(1):377	The H3K9me2 inhibitor BIX01294 mimics the effects of BPA and DEHP on the expression of meiotic genes and Plzf in cultured testes. (A) representative double IF staining for Mvh (green) and Stra8 (red) and Scp3 (red) and (B) Plzf (red) in histological sections of control and BIX01294-treated testes. (C) RT-qPCR analysis of Stra8, Scp3, Rec8, Spo11 and plzf in testes from the control and BIX01294-treated groups. Data are represented as the mean ± SEM. ns, P > 0.05, P < 0.05; *P < 0.01.
S7128	Tazemetostat (EPZ-6438) Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with K_i and IC50 of 2.5 nM and 11 nM in cell-free assays, exhibiting a 35-fold selectivity versus EZH1 and >4,500-fold selectivity relative to 14 other HMTs.	Cancer Cell, 2020, 37(2):157-167 Nat Commun, 2020, 11(1):583 Clin Cancer Res, 2020, 26(1):290-300	EZH2i-induced H3K27ac level change in cancer cells. Cells were treated with 1 mM EPZ-6438 and 1 mM GSK126 for 6 days, respectively. H3K27ac was detected by immunoblotting. Lysates from each cell line were blotted individually. EPZ: EPZ-6438.
S8918^New	MS1943 MS1943 is an orally bioavailable EZH2 selective degrader with IC50 of 120 nM.
S8983^New	MAK683 MAK683 (EED inhibitor-1, example 2) is an inhibitor of embryonic ectoderm development (EED). MAK683 exhibits IC50 of 59 nM, 89 nM and 26 nM in EED Alphascreen binding, LC-MS and ELISA assay, respectively.
S7120	3-deazaneplanocin A (DZNeP) HCl 3-deazaneplanocin A HCl (DZNeP, NSC 617989), an analog of adenosine, is a competitive inhibitor of S-adenosylhomocysteine hydrolase with K_i of 50 pM in a cell-free assay.	Cell Res, 2020, 10.1038/s41422-020-00397-2 Nat Commun, 2020, 11(1):583 J Pathol, 2020, 250(1):79-94	H3K27me3 inhibitors inducing cell differentiation in the MDS-derived erythroid/myeloid cell line and primary MDS bone marrow cells via reducing H3K27me3 and increasing the expressions of PU.1 and its downstream genes. (a) ChIP experiments show a marked decrease in H3K27me3 at the PU.1 enhancer in the OCI-M2 cells treated with DZNep, compared with that in the cells treated with dimethyl sulfoxide (DMSO). (b) RT-PCRs show a significant increase in the expression of PU.1 mRNA in the OCI-M2 cells treated with DZNep in a dose-dependent manner. (c) Flow cytometric studies show that an increase in the expression of glycophorin A/B, a marker associated with erythroid differentiation, in the OCI-M2 cells treated with 0.25 μM of DZNep for 6 days. Red, isotype control; blue, no drug treatment (DMSO only); green, plus drug. (d) Increased PU.1 mRNA expression in primary MDS bone marrow cells treated with DZNep, compared with that in DMSO control. (e) Increased CD18 mRNA expression in primary MDS bone marrow cells treated with DZNep, compared with that in DMSO control. The primary bone marrow cells were from three cytogenetically normal MDS patients, which had marked trilineage dysplasia with varying numbers of blasts (case-1 with 10% blasts, case-2 with 4.6% blasts and case-3 with 11% blasts). The MDS bone marrow cells were treated with 1 μM DZNep or DMSO (control) for 24 h. The levels of PU.1 and CD18 mRNAs were measured by Q-RT-PCRs, while TBP mRNA was used for the internal normalization
S7165	UNC1999 UNC1999 is a potent, orally bioavailable and selective inhibitor of EZH2 and EZH1 with IC50 of 2 nM and 45 nM in cell-free assays, respectively, showing >1000-fold selectivity over a broad range of epigenetic and non-epigenetic targets. UNC1999 is a potent autophagy inducer. UNC1999 specifically suppresses H3K27me3/2 and induces a range of anti-leukemia effects including anti-proliferation, differentiation, and apoptosis.	Anticancer Res, 2020, 40(5):2525-2536 Theranostics, 2020, 10(19):8494-8512 Br J Pharmacol, 2019, 10.1111/bph.14754	Ex vivo growth of the SCLC PDX LX92 is significantly inhibited by the EZH2 inhibitors EPZ-5687, GSK343 and UNC1999 as measured by resazurin conversion (two-way analysis of variance, adjusted for multiple comparisons by the method of Dunnet).
S7265	MM-102 MM-102 is a high-affinity peptidomimetic MLL1 inhibitor with IC50 of 0.4 μM in a cell-free assay.	Mol Carcinog, 2020, 10.1002/mc.23147 Front Genet, 2020, 11:80 Dev Cell, 2019, 49(6):867-881	Immunofluorescence staining of H3K4me2/3 (red) in the IVF, SCNT and MM-102-NT embryos. The nuclei (blue) were stained with DAPI. The merged images of H3K4me2/3 and DNA were purple. Scale bars: 50 μm.
S7079	SGC 0946 SGC 0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM in a cell-free assay, is inactive against a panel of 12 PMTs and DNMT1.	Cancer Cell, 2019, 36(2):179-193 Cell, 2019, 36(2):179-193 Sci Adv, 2019, 5(2):eaav5590
S3147	Entacapone Entacapone (OR-611) inhibits catechol-O-methyltransferase(COMT) with IC50 of 151 nM.
S8071	UNC0638 UNC0638 is a potent, selective and cell-penetrant chemical probe for G9a and GLP histone methyltransferase with IC50 of <15 nM and 19 nM, respectively, shows selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 has anti-viral activities.	Nat Commun, 2020, 11(1):604 Clin Epigenetics, 2019, 11(1):165 Biochim Biophys Acta Gene Regul Mech, 2019, 1862(2):173-183
S8607	JQ-EZ-05 (JQEZ5) JQ-EZ-05 (JQEZ5) is a specific and reversible EZH1/2 inhibitor.	Nat Chem Biol, 2019, 15(4):391-400
S8353	CPI-1205 CPI-1205 is an orally available selective inhibitor of the histone lysine methyltransferase EZH2 with IC50 values of 2 nM and 52 nM for EZH2 and EZH1 respectively. It has potential antineoplastic activity.	Clin Cancer Res, 2019, 10.1158/1078-0432
S7570	UNC0379 UNC0379 is a selective, substrate competitive inhibitor of N-lysine methyltransferase SETD8 with IC50 of 7.9 μM, high selectivity over 15 other methyltransferases.	J Biol Chem, 2020, 10.1074/jbc.RA119.010951 Biochim Biophys Acta Gene Regul Mech, 2019, 1862(2):173-183 Mol Cancer Ther, 2018, 17(7):1585-1594
S7748	EPZ015666(GSK3235025) EPZ015666(GSK3235025) is a potent, selective and orally bioavailable PRMT5 inhibitor with K_i of 5 nM, >20,000-fold selectivity over other PMTs.	Signal Transduct Target Ther, 2020, 5(1):197 Theranostics, 2019, 9(9):2606-2617 EBioMedicine, 2019, 44:98-111	(B) Effect of EPZ015666 on nuclear translocation of p65. Middle panel showed a representative photo of IF staining of p65 localization (green). Nuclei were stained with DAPI.
S8147	MS049 MS049 is a potent and selective inhibitor of PRMT4 and PRMT6 with IC50s of 34 nM and 43 nM, respectively.	EMBO Rep, 2020, 21(2):e48597
S7230	UNC0642 UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.	Clin Epigenetics, 2019, 11(1):165
S8340	SGC2085 SGC2085 is a potent and selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) inhibitor with an IC50 value of 50 nM and >100-fold selective over other PRMTs.
S7294	PFI-2 HCl PFI-2 is a potent, selective, and cell-active lysine methyltransferase SETD7 inhibitor with K_{i (app)} and IC50 of 0.33 nM and 2 nM, 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.	Brain Behav Immun, 2019, 82:382-395 Cell Death Dis, 2018,
S7983	A-196 A-196 is a potent and selective inhibitor of SUV420H1 and SUV420H2 with IC50 values of 0.025 and 0.144 μM, respectively; more than 100-fold selective over other histone methyltransferases and non-epigenetic targets.	J Immunother Cancer, 2019, 7(1):277 Nucleic Acids Res, 2019, 47(21):10977-10993
S4589	Amodiaquine dihydrochloride dihydrate Amodiaquine is a potent, non-competitive inhibitor of histamine N-methyl transferase with estimated Ki of 18.6 nM. It is also used as an antimalarial and anti-inflammatory agent.	J Med Chem, 2020, 31 bioRxiv, 2020, 2020/9/20.4.7.30734
S7820	EPZ020411 2HCl EPZ020411 is a potent and selective small molecule PRMT6 inhibitor with an IC50 of 10 nM.	Theranostics, 2020, 10(1):133-150
S7816	MI-463 MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.
S7832	SGC707 SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3) with IC50 and K_d of 31 nM and 53 nM, respectively.	J Med Chem, 2020, 31 J Immunother Cancer, 2019, 7(1):277
S7817	MI-503 MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. It shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell lines without MLL translocations.	Cancers (Basel), 2020, 12(9)E2715
S8112	MS023 MS023 is a potent, selective, and cell-active Type I PRMT inhibitor with IC50 of 30 nM, 119 nM, 83 nM, 4 nM, and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6 and PRMT8, respectively.	Proteome Sci, 2020, 19;18:6
S8068	Chaetocin Chaetocin, a natural product from Chaetomium species, is a histone methyltransferase inhibitor with IC50 of 0.8 μM, 2.5 μM and 3 μM for dSU(VAR)3-9, mouse G9a and Neurospora crassa DIM5, respectively. Chaetocin is an anticancer agent and inhibitor of thioredoxin reductase (TrxR).	Nat Commun, 2020, 11(1):4709 Front Endocrinol (Lausanne), 2020, 11:323 Nat Commun, 2019, 10(1):273
S5445	AMI-1 (free acid) AMI-1 is a potent and specific Histone Methyltransferase (HMT) inhibitor with IC50 of 3.0 μM and 8.8 μM for yeast Hmt1p and human PRMT1, respectively.
S7619	MI-3 (Menin-MLL Inhibitor) MI-3 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 648 nM.	Clin Epigenetics, 2019, 11(1):137 PLoS Genet, 2016, 12(2):e1005884
S7572	A-366 A-366 is a potent and selective G9a/GLP histone lysine methyltransferase inhibitor with IC50 of 3.3nM, exhibiting >1000-fold selectivity for G9a/GLP over 21 other methyltransferases.	Nat Med, 2019, 25(7):1073-1081 Genome Res, 2019, 29(10):1659-1672
S8664	GSK3326595 (EPZ015938) GSK3326595 (EPZ015938) is an orally active, potent and selective inhibitor of protein arginine methyltransferase 5 (PRMT5) and potently inhibits tumor growth in vitro and in vivo in animal models.	Oncogene, 2019, 38(46):7181-7195 Cancer Med, 2019, 8(5):2414-2428
S7591	BRD4770 BRD4770 is a histone methyltransferase G9a inhibitor with IC50 of 6.3 μM, and induces cell senescence.	Hum Pathol, 2018, 72:117-126
S7805	EPZ011989 EPZ011989 is a potent, selective, orally bioavailable EZH2 inhibitor with K_i of <3 nM.	Cancer Cell, 2019, 36(4):385-401 J Cancer, 2018, 9(20):3787-3796
S8702	EBI-2511 EBI-2511 is a highly potent and orally active EZH2 inhibitor with an IC50 of 4 nM for EZH2(A667G).
S7618	MI-2 (Menin-MLL Inhibitor) MI-2 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 446 nM.	Cell Rep, 2019, 26(2):415-428 Endocrinology, 2019, 10.1210/en.2019-00274 Front Oncol, 2018, 8:632
S7575	LLY-507 LLY-507 is a cell-active, potent, and selective inhibitor of protein-lysine Methyltransferase SMYD2.	Oncol Lett, 2020, 20(5):153 J Immunother Cancer, 2019, 7(1):277 Biochem Biophys Res Commun, 2019, 513(2):340-346
S8111	GSK591 GSK591 (EPZ015866, GSK3203591) is a potent selective inhibitor of the arginine methyltransferase PRMT5 with IC50 of 4 nM.	Elife, 2020, 9e57617 J Immunother Cancer, 2019, 7(1):277 Cancer Med, 2018, 7(3):869-882	Treatment of HCC cells with 500 nmol/L GSK591 for 4 days led to significant loss of PRMT5-catalyzed methylarginine on H4 (H4R3me2s), the upregulation of BTG2, and the phosphorylation of ERK. Inhibition of ERK phosphorylation by PD184352 treatment reversed these effects. H4R3me2s was used to detect the PRMT5 activity. Histone 3 was used as nuclear loading control.
S8209	HLCL-61 HCL HLCL-61 hydrochloride is a potent and selective PRMT5 inhibitor for the treatment of acute myeloid leukemia.	Nat Commun, 2018, 9(1):1572
S8494	PF-06726304 PF-06726304 is a selective EZH2 inhibitor with Ki values of 0.7 nM and 3 nM for WT EZH2 and Y641N respectively; also inhibits H3K27me3 with the IC50 value of 15 nM.
S7611	EI1 EI1 is a potent and selective EZH2 inhibitor with IC50 of 15 nM and 13 nM for EZH2 (WT) and EZH2 (Y641F), respectively.	Mol Cancer, 2017, 10.1186/s12943-016-0575-6 Virology, 2017, 506:34-44 Oncotarget, 2015, 6(32):32410-25	EZH2 inhibitors EI1 or GSK343 are applied in MDA-MB-231 breast cancer cells with NBAT1 over-expression. The invasion suppression effects of NBAT1 was reversed by concomitant EZH2 inhibitors.
S8624	JNJ-64619178 JNJ-64619178 is a PRMT5 inhibitor with high selectivity and potency (subnanomolar range, PRMT5-MEP-50 IC50=0.14 nM) under different in vitro and cellular conditions, paired with favorable pharmacokinetics and safety properties.
S7804	GSK503 GSK503 is a potent and specific EZH2 methyltransferase inhibitor.	Cancer Cell, 2019, 36(4):385-401 J Pathol, 2018, 245(4):433-444 Front Immunol, 2016, 7:496	LC3B‐II levels are increased following 120 h treatment of GSK503 (G, CRMM1 and CRMM2 at 10 μm, and CM2005.1 at 15 μm) or UNC1999 (U, 6 μm).
S7353	EPZ004777 EPZ004777 is a potent, selective DOT1L inhibitor with IC50 of 0.4 nM in a cell-free assay and demonstrates >1,200-fold selectivity for DOT1L over all other tested PMTs. EPZ004777 induces apoptosis.	Nat Chem Biol, 2020, 10.1038/s41589-020-0618-6 Cancer Cell, 2019, 35(5):752-766 Sci Adv, 2019, 5(2):eaav5590	THP-1 cells were treated with MI-3 (6.25 μM, 6 days), GSK126 (5 μM, 6 days), or EPZ004777 (5 μM, 6 days), with orwithout PMA (50 ng/mL, 12 h), and surface expression of CD11b was determined by ﬂow cytometric analysis. The data are representedas the mean ± SD, n = 3. THP-1 cells were collected for Wright-Giemsa staining.
S7061	GSK126 GSK126 (GSK2816126A, GSK2816126) is a potent, highly selective EZH2 methyltransferase inhibitor with IC50 of 9.9 nM, >1000-fold selective for EZH2 over 20 other human methyltransferases.	Nat Genet, 2020, 52(4):408-417 J Clin Invest, 2020, 3;130(2):853-862 Nat Commun, 2020, 11(1):3018	(C) Four GCBDLBCL cells lines [1 wild-type (wt), 3 mutated (mut) EZH2] were treated with 500 nmol/l BAY 1238097 or with an EZH2 inhibitor (DZNep and GSK126, both used at the concentration of 500 nmol/l) as single agents and in combination for 72 h. The arrow indicates the EZH2 correct band. Dimethyl sulphoxide (DMSO) alone was added as negative control cells. Membranes were hybridized with antibodies against EZH2, H3K27me3, histone H3 and GAPDH.
S7656	CPI-360 CPI-360 is a potent, selective,and SAM-competitive EZH1 inhibitor with IC50 of 102.3 nM, >100-fold selectivity over other methyltransferases.
S7616	CPI-169 CPI-169 is a potent, and selective EZH2 inhibitor with IC50 of 0.24 nM, 0.51 nM, and 6.1 nM for EZH2 WT, EZH2 Y641N, and EZH1, respectively.	J Clin Invest, 2020, 134217 Nat Commun, 2018, 9(1):4116 Virology, 2017, 506:34-44
S7884	AMI-1 AMI-1 is a potent and specific Histone Methyltransferase (HMT) inhibitor with IC50 of 3.0 μM and 8.8 μM for yeast Hmt1p and human PRMT1, respectively.	Cell Rep, 2018, 24(12):3207-3223 Nitric Oxide, 2017, 67:58-67	Effects of microinjection of AMI-1 into the RVLM on cardiovascular activity in the Ang II-induced hypertensive rats. The representative original tracings (A)
S7815	MI-136 MI-136 can specifically inhibit the menin-MLL interaction. It inhibits DHT-induced expression of androgen receptor (AR) target genes.	J Med Chem, 2020, 31
S2184^New	WDR5-0103 WDR5-0103 (WD-Repeat Protein 5-0103) is a small-molecule antagonist of WDR5 (WD40 repeat protein 5) with Kd of 450 nM.
S7833	OICR-9429 OICR-9429 is a potent antagonist of the interaction of WDR5 with peptide regions of MLL and Histone 3 and reduces viability of acute myeloid leukemia cells in vitro. It binds to WDR5 with high affinity (KD = 93 ± 28 nM.	Theranostics, 2018, 8(18):5143-5158	(F) Real-time PCR analysis showed the VEGFA mRNA expression in the HOXC10-overexpressing glioma cells treated with vehicle or 1 μM OICR-9429 for 2 days. (G) ChIP-qPCR enrichments of H3K4me3, polymerase II or IgG on VEGFA promoter region 3 in the HOXC10-overexpressing glioma cells treated with vehicle or 1 μM OICR-9429 for 2 days. All the assays shown in the figure were independently replicated three times. Error bars, SD. * P < 0.05.
S8359	UNC3866 UNC3866 is a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K(d) of ∼100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains.
S8496	EED226 EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED.	Nat Commun, 2020, 11(1):3018 J Med Chem, 2020, 31 Cell Stem Cell, 2019, 24(1):123-137

Catalog No.	Information	Product Use Citations	Product Validations
S7062	Pinometostat (EPZ5676) Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with K_i of 80 pM in a cell-free assay, demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor. Phase 1.	Nat Cell Biol, 2020, 11 Mol Brain, 2020, 29;13(1):85 Biosci Rep, 2020, 31;40(1):BSR20193515	Treatment of c-Kit+ bone marrow (BM) cells from Setd2^f/f/Vav1-Cre mice with JQ1 500nM, EPZ-5676 1uM, BAY 1143572 400 nM for 24 h. Then cells were collected to determine the proteins levels of RNA pol II (Ser2P), pol II (Ser5P), Gata1, Gata3, Myc, and β-actin by immunoblotting.
S7004	EPZ005687 EPZ005687 is a potent and selective inhibitor of EZH2 with K_i of 24 nM in a cell-free assay, 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.	Nat Commun, 2020, 11(1):604 Gastric Cancer, 2020, 10.1007/s10120-020-01094-0 Theranostics, 2020, 10(19):8494-8512	Western blot analysis of day 7 lysates from LX92 lysates treated with various EZH2 inhibitors.
S7164	GSK343 GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. GSK343 induces autophagy.	Nat Commun, 2020, 11(1):3018 Gastric Cancer, 2020, 10.1007/s10120-020-01094-0 Am J Cancer Res, 2020, 1;10(4):1194-1206 eCollection 2020	Representative confocal microscopy images of oocytes with DZNep or GSK343 treatment. The oocytes presented with a typical barrel-shaped spindle and well-aligned chromosomes on the metaphase plate not only in DZNep or GSK343 treated group but also in the control group. Spindle was recognized by α-tubulin (green) and DNA was recognized by PI (Propidium iodide, red). Scale bar = 4 μm.
S8006	BIX 01294 BIX01294 is an inhibitor of G9a histone methyltransferase with IC50 of 2.7 μM in a cell-free assay, reduces H3K9me2 of bulk histones, also weakly inhibits GLP (primarily H3K9me3), no significant activity observed at other histone methyltransferases. BIX01294 induces autophagy.	Nat Commun, 2020, 11(1):604 Oxid Med Cell Longev, 2020, 12;2020:6983268 Sci Rep, 2020, 10(1):377	The H3K9me2 inhibitor BIX01294 mimics the effects of BPA and DEHP on the expression of meiotic genes and Plzf in cultured testes. (A) representative double IF staining for Mvh (green) and Stra8 (red) and Scp3 (red) and (B) Plzf (red) in histological sections of control and BIX01294-treated testes. (C) RT-qPCR analysis of Stra8, Scp3, Rec8, Spo11 and plzf in testes from the control and BIX01294-treated groups. Data are represented as the mean ± SEM. ns, P > 0.05, P < 0.05; *P < 0.01.
S7128	Tazemetostat (EPZ-6438) Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with K_i and IC50 of 2.5 nM and 11 nM in cell-free assays, exhibiting a 35-fold selectivity versus EZH1 and >4,500-fold selectivity relative to 14 other HMTs.	Cancer Cell, 2020, 37(2):157-167 Nat Commun, 2020, 11(1):583 Clin Cancer Res, 2020, 26(1):290-300	EZH2i-induced H3K27ac level change in cancer cells. Cells were treated with 1 mM EPZ-6438 and 1 mM GSK126 for 6 days, respectively. H3K27ac was detected by immunoblotting. Lysates from each cell line were blotted individually. EPZ: EPZ-6438.
S8918^New	MS1943 MS1943 is an orally bioavailable EZH2 selective degrader with IC50 of 120 nM.
S8983^New	MAK683 MAK683 (EED inhibitor-1, example 2) is an inhibitor of embryonic ectoderm development (EED). MAK683 exhibits IC50 of 59 nM, 89 nM and 26 nM in EED Alphascreen binding, LC-MS and ELISA assay, respectively.
S7120	3-deazaneplanocin A (DZNeP) HCl 3-deazaneplanocin A HCl (DZNeP, NSC 617989), an analog of adenosine, is a competitive inhibitor of S-adenosylhomocysteine hydrolase with K_i of 50 pM in a cell-free assay.	Cell Res, 2020, 10.1038/s41422-020-00397-2 Nat Commun, 2020, 11(1):583 J Pathol, 2020, 250(1):79-94	H3K27me3 inhibitors inducing cell differentiation in the MDS-derived erythroid/myeloid cell line and primary MDS bone marrow cells via reducing H3K27me3 and increasing the expressions of PU.1 and its downstream genes. (a) ChIP experiments show a marked decrease in H3K27me3 at the PU.1 enhancer in the OCI-M2 cells treated with DZNep, compared with that in the cells treated with dimethyl sulfoxide (DMSO). (b) RT-PCRs show a significant increase in the expression of PU.1 mRNA in the OCI-M2 cells treated with DZNep in a dose-dependent manner. (c) Flow cytometric studies show that an increase in the expression of glycophorin A/B, a marker associated with erythroid differentiation, in the OCI-M2 cells treated with 0.25 μM of DZNep for 6 days. Red, isotype control; blue, no drug treatment (DMSO only); green, plus drug. (d) Increased PU.1 mRNA expression in primary MDS bone marrow cells treated with DZNep, compared with that in DMSO control. (e) Increased CD18 mRNA expression in primary MDS bone marrow cells treated with DZNep, compared with that in DMSO control. The primary bone marrow cells were from three cytogenetically normal MDS patients, which had marked trilineage dysplasia with varying numbers of blasts (case-1 with 10% blasts, case-2 with 4.6% blasts and case-3 with 11% blasts). The MDS bone marrow cells were treated with 1 μM DZNep or DMSO (control) for 24 h. The levels of PU.1 and CD18 mRNAs were measured by Q-RT-PCRs, while TBP mRNA was used for the internal normalization
S7165	UNC1999 UNC1999 is a potent, orally bioavailable and selective inhibitor of EZH2 and EZH1 with IC50 of 2 nM and 45 nM in cell-free assays, respectively, showing >1000-fold selectivity over a broad range of epigenetic and non-epigenetic targets. UNC1999 is a potent autophagy inducer. UNC1999 specifically suppresses H3K27me3/2 and induces a range of anti-leukemia effects including anti-proliferation, differentiation, and apoptosis.	Anticancer Res, 2020, 40(5):2525-2536 Theranostics, 2020, 10(19):8494-8512 Br J Pharmacol, 2019, 10.1111/bph.14754	Ex vivo growth of the SCLC PDX LX92 is significantly inhibited by the EZH2 inhibitors EPZ-5687, GSK343 and UNC1999 as measured by resazurin conversion (two-way analysis of variance, adjusted for multiple comparisons by the method of Dunnet).
S7265	MM-102 MM-102 is a high-affinity peptidomimetic MLL1 inhibitor with IC50 of 0.4 μM in a cell-free assay.	Mol Carcinog, 2020, 10.1002/mc.23147 Front Genet, 2020, 11:80 Dev Cell, 2019, 49(6):867-881	Immunofluorescence staining of H3K4me2/3 (red) in the IVF, SCNT and MM-102-NT embryos. The nuclei (blue) were stained with DAPI. The merged images of H3K4me2/3 and DNA were purple. Scale bars: 50 μm.
S7079	SGC 0946 SGC 0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM in a cell-free assay, is inactive against a panel of 12 PMTs and DNMT1.	Cancer Cell, 2019, 36(2):179-193 Cell, 2019, 36(2):179-193 Sci Adv, 2019, 5(2):eaav5590
S3147	Entacapone Entacapone (OR-611) inhibits catechol-O-methyltransferase(COMT) with IC50 of 151 nM.
S8071	UNC0638 UNC0638 is a potent, selective and cell-penetrant chemical probe for G9a and GLP histone methyltransferase with IC50 of <15 nM and 19 nM, respectively, shows selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 has anti-viral activities.	Nat Commun, 2020, 11(1):604 Clin Epigenetics, 2019, 11(1):165 Biochim Biophys Acta Gene Regul Mech, 2019, 1862(2):173-183
S8607	JQ-EZ-05 (JQEZ5) JQ-EZ-05 (JQEZ5) is a specific and reversible EZH1/2 inhibitor.	Nat Chem Biol, 2019, 15(4):391-400
S8353	CPI-1205 CPI-1205 is an orally available selective inhibitor of the histone lysine methyltransferase EZH2 with IC50 values of 2 nM and 52 nM for EZH2 and EZH1 respectively. It has potential antineoplastic activity.	Clin Cancer Res, 2019, 10.1158/1078-0432
S7570	UNC0379 UNC0379 is a selective, substrate competitive inhibitor of N-lysine methyltransferase SETD8 with IC50 of 7.9 μM, high selectivity over 15 other methyltransferases.	J Biol Chem, 2020, 10.1074/jbc.RA119.010951 Biochim Biophys Acta Gene Regul Mech, 2019, 1862(2):173-183 Mol Cancer Ther, 2018, 17(7):1585-1594
S7748	EPZ015666(GSK3235025) EPZ015666(GSK3235025) is a potent, selective and orally bioavailable PRMT5 inhibitor with K_i of 5 nM, >20,000-fold selectivity over other PMTs.	Signal Transduct Target Ther, 2020, 5(1):197 Theranostics, 2019, 9(9):2606-2617 EBioMedicine, 2019, 44:98-111	(B) Effect of EPZ015666 on nuclear translocation of p65. Middle panel showed a representative photo of IF staining of p65 localization (green). Nuclei were stained with DAPI.
S8147	MS049 MS049 is a potent and selective inhibitor of PRMT4 and PRMT6 with IC50s of 34 nM and 43 nM, respectively.	EMBO Rep, 2020, 21(2):e48597
S7230	UNC0642 UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.	Clin Epigenetics, 2019, 11(1):165
S8340	SGC2085 SGC2085 is a potent and selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) inhibitor with an IC50 value of 50 nM and >100-fold selective over other PRMTs.
S7294	PFI-2 HCl PFI-2 is a potent, selective, and cell-active lysine methyltransferase SETD7 inhibitor with K_{i (app)} and IC50 of 0.33 nM and 2 nM, 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.	Brain Behav Immun, 2019, 82:382-395 Cell Death Dis, 2018,
S7983	A-196 A-196 is a potent and selective inhibitor of SUV420H1 and SUV420H2 with IC50 values of 0.025 and 0.144 μM, respectively; more than 100-fold selective over other histone methyltransferases and non-epigenetic targets.	J Immunother Cancer, 2019, 7(1):277 Nucleic Acids Res, 2019, 47(21):10977-10993
S4589	Amodiaquine dihydrochloride dihydrate Amodiaquine is a potent, non-competitive inhibitor of histamine N-methyl transferase with estimated Ki of 18.6 nM. It is also used as an antimalarial and anti-inflammatory agent.	J Med Chem, 2020, 31 bioRxiv, 2020, 2020/9/20.4.7.30734
S7820	EPZ020411 2HCl EPZ020411 is a potent and selective small molecule PRMT6 inhibitor with an IC50 of 10 nM.	Theranostics, 2020, 10(1):133-150
S7816	MI-463 MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.
S7832	SGC707 SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3) with IC50 and K_d of 31 nM and 53 nM, respectively.	J Med Chem, 2020, 31 J Immunother Cancer, 2019, 7(1):277
S7817	MI-503 MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. It shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell lines without MLL translocations.	Cancers (Basel), 2020, 12(9)E2715
S8112	MS023 MS023 is a potent, selective, and cell-active Type I PRMT inhibitor with IC50 of 30 nM, 119 nM, 83 nM, 4 nM, and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6 and PRMT8, respectively.	Proteome Sci, 2020, 19;18:6
S8068	Chaetocin Chaetocin, a natural product from Chaetomium species, is a histone methyltransferase inhibitor with IC50 of 0.8 μM, 2.5 μM and 3 μM for dSU(VAR)3-9, mouse G9a and Neurospora crassa DIM5, respectively. Chaetocin is an anticancer agent and inhibitor of thioredoxin reductase (TrxR).	Nat Commun, 2020, 11(1):4709 Front Endocrinol (Lausanne), 2020, 11:323 Nat Commun, 2019, 10(1):273
S5445	AMI-1 (free acid) AMI-1 is a potent and specific Histone Methyltransferase (HMT) inhibitor with IC50 of 3.0 μM and 8.8 μM for yeast Hmt1p and human PRMT1, respectively.
S7619	MI-3 (Menin-MLL Inhibitor) MI-3 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 648 nM.	Clin Epigenetics, 2019, 11(1):137 PLoS Genet, 2016, 12(2):e1005884
S7572	A-366 A-366 is a potent and selective G9a/GLP histone lysine methyltransferase inhibitor with IC50 of 3.3nM, exhibiting >1000-fold selectivity for G9a/GLP over 21 other methyltransferases.	Nat Med, 2019, 25(7):1073-1081 Genome Res, 2019, 29(10):1659-1672
S8664	GSK3326595 (EPZ015938) GSK3326595 (EPZ015938) is an orally active, potent and selective inhibitor of protein arginine methyltransferase 5 (PRMT5) and potently inhibits tumor growth in vitro and in vivo in animal models.	Oncogene, 2019, 38(46):7181-7195 Cancer Med, 2019, 8(5):2414-2428
S7591	BRD4770 BRD4770 is a histone methyltransferase G9a inhibitor with IC50 of 6.3 μM, and induces cell senescence.	Hum Pathol, 2018, 72:117-126
S7805	EPZ011989 EPZ011989 is a potent, selective, orally bioavailable EZH2 inhibitor with K_i of <3 nM.	Cancer Cell, 2019, 36(4):385-401 J Cancer, 2018, 9(20):3787-3796
S8702	EBI-2511 EBI-2511 is a highly potent and orally active EZH2 inhibitor with an IC50 of 4 nM for EZH2(A667G).
S7618	MI-2 (Menin-MLL Inhibitor) MI-2 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 446 nM.	Cell Rep, 2019, 26(2):415-428 Endocrinology, 2019, 10.1210/en.2019-00274 Front Oncol, 2018, 8:632
S7575	LLY-507 LLY-507 is a cell-active, potent, and selective inhibitor of protein-lysine Methyltransferase SMYD2.	Oncol Lett, 2020, 20(5):153 J Immunother Cancer, 2019, 7(1):277 Biochem Biophys Res Commun, 2019, 513(2):340-346
S8111	GSK591 GSK591 (EPZ015866, GSK3203591) is a potent selective inhibitor of the arginine methyltransferase PRMT5 with IC50 of 4 nM.	Elife, 2020, 9e57617 J Immunother Cancer, 2019, 7(1):277 Cancer Med, 2018, 7(3):869-882	Treatment of HCC cells with 500 nmol/L GSK591 for 4 days led to significant loss of PRMT5-catalyzed methylarginine on H4 (H4R3me2s), the upregulation of BTG2, and the phosphorylation of ERK. Inhibition of ERK phosphorylation by PD184352 treatment reversed these effects. H4R3me2s was used to detect the PRMT5 activity. Histone 3 was used as nuclear loading control.
S8209	HLCL-61 HCL HLCL-61 hydrochloride is a potent and selective PRMT5 inhibitor for the treatment of acute myeloid leukemia.	Nat Commun, 2018, 9(1):1572
S8494	PF-06726304 PF-06726304 is a selective EZH2 inhibitor with Ki values of 0.7 nM and 3 nM for WT EZH2 and Y641N respectively; also inhibits H3K27me3 with the IC50 value of 15 nM.
S7611	EI1 EI1 is a potent and selective EZH2 inhibitor with IC50 of 15 nM and 13 nM for EZH2 (WT) and EZH2 (Y641F), respectively.	Mol Cancer, 2017, 10.1186/s12943-016-0575-6 Virology, 2017, 506:34-44 Oncotarget, 2015, 6(32):32410-25	EZH2 inhibitors EI1 or GSK343 are applied in MDA-MB-231 breast cancer cells with NBAT1 over-expression. The invasion suppression effects of NBAT1 was reversed by concomitant EZH2 inhibitors.
S8624	JNJ-64619178 JNJ-64619178 is a PRMT5 inhibitor with high selectivity and potency (subnanomolar range, PRMT5-MEP-50 IC50=0.14 nM) under different in vitro and cellular conditions, paired with favorable pharmacokinetics and safety properties.
S7804	GSK503 GSK503 is a potent and specific EZH2 methyltransferase inhibitor.	Cancer Cell, 2019, 36(4):385-401 J Pathol, 2018, 245(4):433-444 Front Immunol, 2016, 7:496	LC3B‐II levels are increased following 120 h treatment of GSK503 (G, CRMM1 and CRMM2 at 10 μm, and CM2005.1 at 15 μm) or UNC1999 (U, 6 μm).
S7353	EPZ004777 EPZ004777 is a potent, selective DOT1L inhibitor with IC50 of 0.4 nM in a cell-free assay and demonstrates >1,200-fold selectivity for DOT1L over all other tested PMTs. EPZ004777 induces apoptosis.	Nat Chem Biol, 2020, 10.1038/s41589-020-0618-6 Cancer Cell, 2019, 35(5):752-766 Sci Adv, 2019, 5(2):eaav5590	THP-1 cells were treated with MI-3 (6.25 μM, 6 days), GSK126 (5 μM, 6 days), or EPZ004777 (5 μM, 6 days), with orwithout PMA (50 ng/mL, 12 h), and surface expression of CD11b was determined by ﬂow cytometric analysis. The data are representedas the mean ± SD, n = 3. THP-1 cells were collected for Wright-Giemsa staining.
S7061	GSK126 GSK126 (GSK2816126A, GSK2816126) is a potent, highly selective EZH2 methyltransferase inhibitor with IC50 of 9.9 nM, >1000-fold selective for EZH2 over 20 other human methyltransferases.	Nat Genet, 2020, 52(4):408-417 J Clin Invest, 2020, 3;130(2):853-862 Nat Commun, 2020, 11(1):3018	(C) Four GCBDLBCL cells lines [1 wild-type (wt), 3 mutated (mut) EZH2] were treated with 500 nmol/l BAY 1238097 or with an EZH2 inhibitor (DZNep and GSK126, both used at the concentration of 500 nmol/l) as single agents and in combination for 72 h. The arrow indicates the EZH2 correct band. Dimethyl sulphoxide (DMSO) alone was added as negative control cells. Membranes were hybridized with antibodies against EZH2, H3K27me3, histone H3 and GAPDH.
S7656	CPI-360 CPI-360 is a potent, selective,and SAM-competitive EZH1 inhibitor with IC50 of 102.3 nM, >100-fold selectivity over other methyltransferases.
S7616	CPI-169 CPI-169 is a potent, and selective EZH2 inhibitor with IC50 of 0.24 nM, 0.51 nM, and 6.1 nM for EZH2 WT, EZH2 Y641N, and EZH1, respectively.	J Clin Invest, 2020, 134217 Nat Commun, 2018, 9(1):4116 Virology, 2017, 506:34-44
S7884	AMI-1 AMI-1 is a potent and specific Histone Methyltransferase (HMT) inhibitor with IC50 of 3.0 μM and 8.8 μM for yeast Hmt1p and human PRMT1, respectively.	Cell Rep, 2018, 24(12):3207-3223 Nitric Oxide, 2017, 67:58-67	Effects of microinjection of AMI-1 into the RVLM on cardiovascular activity in the Ang II-induced hypertensive rats. The representative original tracings (A)
S7815	MI-136 MI-136 can specifically inhibit the menin-MLL interaction. It inhibits DHT-induced expression of androgen receptor (AR) target genes.	J Med Chem, 2020, 31

Catalog No.	Information	Product Use Citations	Product Validations
S2184^New	WDR5-0103 WDR5-0103 (WD-Repeat Protein 5-0103) is a small-molecule antagonist of WDR5 (WD40 repeat protein 5) with Kd of 450 nM.
S7833	OICR-9429 OICR-9429 is a potent antagonist of the interaction of WDR5 with peptide regions of MLL and Histone 3 and reduces viability of acute myeloid leukemia cells in vitro. It binds to WDR5 with high affinity (KD = 93 ± 28 nM.	Theranostics, 2018, 8(18):5143-5158	(F) Real-time PCR analysis showed the VEGFA mRNA expression in the HOXC10-overexpressing glioma cells treated with vehicle or 1 μM OICR-9429 for 2 days. (G) ChIP-qPCR enrichments of H3K4me3, polymerase II or IgG on VEGFA promoter region 3 in the HOXC10-overexpressing glioma cells treated with vehicle or 1 μM OICR-9429 for 2 days. All the assays shown in the figure were independently replicated three times. Error bars, SD. * P < 0.05.
S8359	UNC3866 UNC3866 is a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K(d) of ∼100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains.

Catalog No.

Information

Product Use Citations

Product Validations

S2184^New

WDR5-0103

WDR5-0103 (WD-Repeat Protein 5-0103) is a small-molecule antagonist of WDR5 (WD40 repeat protein 5) with Kd of 450 nM.

S7833

OICR-9429 is a potent antagonist of the interaction of WDR5 with peptide regions of MLL and Histone 3 and reduces viability of acute myeloid leukemia cells in vitro. It binds to WDR5 with high affinity (KD = 93 ± 28 nM.

Theranostics, 2018, 8(18):5143-5158

S8359

UNC3866

UNC3866 is a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K(d) of ∼100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains.

Catalog No.	Information	Product Use Citations	Product Validations
S8496	EED226 EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED.	Nat Commun, 2020, 11(1):3018 J Med Chem, 2020, 31 Cell Stem Cell, 2019, 24(1):123-137

Catalog No.

Information

Product Use Citations

Product Validations

S8496

EED226

EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED.

Nat Commun, 2020, 11(1):3018

J Med Chem, 2020, 31

Cell Stem Cell, 2019, 24(1):123-137

Choose Your Country or Region

By Signaling Pathways

By product type

Histone Methyltransferase

Signaling Pathway Map

Research Area

Inhibitory Selectivity

Histone Methyltransferase Products