Histone Methyltransferase

Signaling Pathway

Histone Methyltransferase Signaling Pathway

Histone Methyltransferase Products

  • All (61)
  • Histone Methyltransferase Inhibitors (57)
  • Histone Methyltransferase Antagonists (3)
  • New Histone Methyltransferase Products
Catalog No. Product Name Information Product Use Citations Product Validations
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.
Signal Transduct Target Ther, 2024, 9(1):2
Cell, 2023, 186(13):2765-2782.e28
Mol Cancer, 2023, 22(1):85
S7128 Tazemetostat (EPZ-6438) Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with Ki 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.
Signal Transduct Target Ther, 2024, 9(1):2
Nat Commun, 2024, 15(1):1367
Sci Rep, 2024, 14(1):4303
S7120 DZNeP (3-deazaneplanocin A) HCl DZNeP (3-deazaneplanocin A) HCl, an analog of adenosine, is a competitive inhibitor of S-adenosylhomocysteine hydrolase with Ki of 50 pM in a cell-free assay.
Mol Cancer, 2023, 22(1):85
Cell Stem Cell, 2023, 30(9):1235-1245.e6
Nat Commun, 2023, 14(1):4062
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.
J Immunother Cancer, 2023, 11(11)e007736
Clin Transl Med, 2023, 13(12):e1502
J Neuroinflammation, 2023, 20(1):168
S7062 Pinometostat (EPZ5676) Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with Ki 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.
Exp Hematol Oncol, 2023, 12(1):81
EMBO Rep, 2023, e56233.
Life Sci Alliance, 2023, 6(5)e202201619
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. BIX01294 also inhibits H3K36 methylation by oncoproteins NSD1, NSD2 and NSD3.
Dev Cell, 2023, 58(6):506-521.e5
Cell Death Dis, 2023, 14(9):627
Cell Death Dis, 2023, 14(9):627
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.
Cell Rep, 2023, 42(8):112885
Cell Rep, 2023, 42(6):112566
Int J Mol Sci, 2023, 24(11)9365
S7748 EPZ015666 (GSK3235025) EPZ015666 (GSK3235025) is a potent, selective and orally bioavailable PRMT5 inhibitor with Ki of 5 nM, >20,000-fold selectivity over other PMTs.
Nat Commun, 2023, 14(1):4003
Mol Cell, 2023, 83(15):2810-2828.e6
Cell Rep Med, 2023, 4(12):101326
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.
Acta Pharm Sin B, 2023, 13(6):2601-2612
J Exp Clin Cancer Res, 2023, 42(1):320
Pharmacol Res, 2022, 177:106122
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.
Elife, 2023, 12e85365
Open Biol, 2023, 13(1):220211
Nat Commun, 2022, 13(1):4199
S7004 EPZ005687 EPZ005687 is a potent and selective inhibitor of EZH2 with Ki of 24 nM in a cell-free assay, 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.
J Exp Clin Cancer Res, 2023, 42(1):320
BMC Med, 2022, 20(1):189
Cancers (Basel), 2022, 15(1)208
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).
Cancer Cell, 2023, 41(6):1118-1133.e12
Mol Ther, 2023, 10.1016/j.ymthe.2023.11.012
Clin Cancer Res, 2023, 29(1):271-278
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.
bioRxiv, 2024, 2024.02.06.579191
Cell Rep, 2023, 42(8):112885
Cell Rep, 2023, 42(6):112566
S8664 Pemrametostat (GSK3326595) Pemrametostat (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.
NPJ Precis Oncol, 2024, 8(1):52
Nat Metab, 2023, 10.1038/s42255-023-00861-4
Nat Metab, 2023, 5(9):1544-1562
S7265 MM-102 MM-102 (HMTase Inhibitor IX) is a high-affinity peptidomimetic inhibitor of the WDR5/MLL1 protein-protein interaction, which bind to WDR5 with Ki < 1 nM and IC50 =2.4nM.
Life Sci Alliance, 2023, 6(5)e202201619
Cell Stem Cell, 2022, S1934-5909(22)00417-9
Cell Rep, 2022, 39(7):110836
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.
Cell Rep, 2024, 43(2):113779
Cell Rep, 2023, 42(6):112566
Cancer Cell, 2022, 40(10):1190-1206.e9
S7805 EPZ011989 EPZ011989 is a potent, selective, orally bioavailable EZH2 inhibitor with Ki of <3 nM.
Cancers (Basel), 2024, 16(3):569.
Cancers (Basel), 2024, 16(3)569
Nat Cell Biol, 2023, 25(2):258-272
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.
Cell Rep, 2024, 43(1):113575
Cancers (Basel), 2023, 15(8)2199
bioRxiv, 2023, 2023.07.11.548643
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.
J Clin Invest, 2023, 133(13)e169993
EBioMedicine, 2023, 92:104602
Cell Rep, 2023, 42(9):113145
S7570 UNC0379 UNC0379 is a selective, substrate competitive inhibitor of N-lysine methyltransferase SETD8 with IC50 of 7.3 μM, high selectivity over 15 other methyltransferases.
Cell Death Dis, 2023, 10.1038/s41419-023-06167-3
Cell Death Dis, 2023, 14(9):638
Cell Biosci, 2023, 13(1):107
S8111 GSK591 GSK591 (EPZ015866, GSK3203591) is a potent selective inhibitor of the arginine methyltransferase PRMT5 with IC50 of 4 nM.
Int J Mol Sci, 2023, 24(5)4327
Proc Natl Acad Sci U S A, 2022, 119(43):e2205255119
Hepatology, 2021, 10.1002/hep.32245
S8353 Lirametostat (CPI-1205) Lirametostat (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.
JCI Insight, 2022, e155899
Cancer Discov, 2021, candisc.0913.2020
Nat Commun, 2021, 12(1):6276
S7618 MI-2 (Menin-MLL Inhibitor) MI-2 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 446 nM.
Cell Stem Cell, 2022, S1934-5909(22)00417-9
Life Sci Alliance, 2022, 5(4)e202101187
J Immunol, 2021, ji1901348
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 Exp Clin Cancer Res, 2023, 42(1):96
Nat Commun, 2022, 13(1):6226
Nat Commun, 2022, 13(1):6226
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.
Nat Cell Biol, 2023, 25(2):258-272
J Clin Invest, 2023, 133(13)e169993
Breast Cancer Res, 2022, 24(1):52
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.
Sci Rep, 2024, 14(1):4303
Journal of Pharmacological Sciences, 2024, Pages 209-217
Nat Commun, 2023, 14(1):2806
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.
iScience, 2023, 26(3):106158
Cancer Res, 2022, 82(8):1534-1547
Sci Total Environ, 2022, 838(Pt 1):155713
S7804 GSK503 GSK503 is a potent and specific EZH2 methyltransferase inhibitor.
Int J Mol Sci, 2023, 24(10)8603
Cancer Res, 2022, CAN-22-0736
Front Genet, 2022, 13:1013475
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 Death Dis, 2023, 14(4):233
Oncogenesis, 2022, 11(1):45
Oncogene, 2021, 40(7):1375-1389
S7294 PFI-2 HCl PFI-2 is a potent, selective, and cell-active lysine methyltransferase SETD7 inhibitor with Ki (app) and IC50 of 0.33 nM and 2 nM, 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.
Life Sci Alliance, 2023, 6(5)e202201619
Pharmacol Res, 2022, 177:106122
Cell Rep, 2022, 39(12):110994
S7832 SGC707 SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3) with IC50 and Kd of 31 nM and 53 nM, respectively.
Cell Death Dis, 2022, 13(11):943
J Med Chem, 2020, 31
Transpl Int, 2020, 33(2):229-243
S7572 A-366 A-366 is a potent and selective G9a/GLP histone lysine methyltransferase inhibitor with IC50 of 3.3nM and 38nM, exhibiting >1000-fold selectivity for G9a/GLP over 21 other methyltransferases.
Cell Rep, 2024, 43(1):113575
Cancers (Basel), 2023, 15(8)2199
Cancer Cell, 2022, 40(10):1190-1206.e9
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.
Cell Death Differ, 2023, 10.1038/s41418-023-01167-4
Nat Biomed Eng, 2021, 10.1038/s41551-021-00718-9
J Med Chem, 2020, 31
S7619 MI-3 (Menin-MLL Inhibitor) MI-3 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 648 nM.
Nat Commun, 2023, 14(1):3062
Nature, 2021, 10.1038/s41586-021-04116-8
Clin Epigenetics, 2019, 11(1):137
S7591 BRD4770 BRD4770 is a histone methyltransferase G9a inhibitor with IC50 of 6.3 μM, and induces cell senescence.
Hum Cell, 2023, 10.1007/s13577-023-00924-4
Cell Insight, 2023, 2(4):100112
Pharmacol Res, 2022, 177:106122
S7575 LLY-507 LLY-507 is a cell-active, potent, and selective inhibitor of protein-lysine Methyltransferase SMYD2.
Pharmacol Res, 2022, 177:106122
Oncol Lett, 2020, 20(5):153
J Immunother Cancer, 2019, 7(1):277
S8624 Onametostat (JNJ-64619178) Onametostat (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.
Sci Rep, 2024, 14(1):4303
Nat Commun, 2023, 14(1):1078
J Immunother Cancer, 2023, 11(6)e006890
S2184 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.
J Clin Invest, 2023, 133(13)e169993
Cell Rep, 2023, 42(9):113145
Biomed Pharmacother, 2022, 154:113663
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.
Cancer Res, 2018, 78(20):5731-5740
Mol Cancer, 2017, 10.1186/s12943-016-0575-6
Virology, 2017, 506:34-44
S4021 Tolcapone Tolcapone (Ro 40-7592) is a selective, potent and reversible of catechol-O-methyl transferase (COMT) inhibitor with Ki of 30 nM.
FASEB J, 2022, 36(7):e22399
Viruses, 2021, 13(8)1533
Front Bioinform, 2021, 1:710591
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.
Leukemia, 2021, 10.1038/s41375-021-01121-8
Leukemia, 2021, 10.1038/s41375-021-01121-8
Int J Mol Sci, 2021, 22(2)E619
S7820 EPZ020411 2HCl EPZ020411 is a potent and selective small molecule PRMT6 inhibitor with an IC50 of 10 nM.
Nat Commun, 2023, 14(1):1430
Inflamm Res, 2022, 71(3):309-320
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.
J Clin Invest, 2023, 133(13)e169993
iScience, 2023, 26(10):107726
Front Oncol, 2020, 10:524922
S8209 HLCL-61 HCL HLCL-61 hydrochloride is a potent and selective PRMT5 inhibitor for the treatment of acute myeloid leukemia.
Front Immunol, 2019, 10:174
Nat Commun, 2018, 9(1):1572
Cancer Res, 2018, 78(20):5731-5740
S8983 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.
PLoS Biol, 2023, 21(4):e3002038
Cell Death Dis, 2022, 13(2):155
JCI Insight, 2022, e155899
S7815 MI-136 MI-136 can specifically inhibit the menin-MLL interaction. It inhibits DHT-induced expression of androgen receptor (AR) target genes.
Breast Cancer Res, 2022, 24(1):52
Cancer Cell Int, 2022, 22(1):336
J Med Chem, 2020, 31
S3147 Entacapone Entacapone (OR-611) inhibits catechol-O-methyltransferase(COMT) with IC50 of 151 nM. Entacapone can be used for the research of Parkinson's disease. Entacapone serves as a inhibitor of FTO demethylation with an IC50 of 3.5 μM, can be used for the research of metabolic disorders.
Elife, 2022, 11e72668
bioRxiv, 2021, 10.1101/2021.03.22.436393
S8147 MS049 MS049 is a potent and selective inhibitor of PRMT4 and PRMT6 with IC50s of 34 nM and 43 nM, respectively.
Research Square, 2021, 10.21203/rs.3.rs-620216/v1
EMBO Rep, 2020, 21(2):e48597
S7868 SAH (S-Adenosyl-L-homocysteine) SAH (S-Adenosyl-L-homocysteine) is an inhibitor for (Methyltransferase Like 3-14) METTL3-METTL14 heterodimer complex (METTL3-14) with IC50 of 0.9 μM.
Clin Epigenetics, 2024, 16(1):18
Heliyon, 2023, 9(6):e16905
J Pept Sci, 2022, e3456.
S8934 VTP50469 VTP50469 is a potent, highly selective and orally active inhibitor of Menin-MLL interaction with Ki of 104 pM. VTP50469 exhibits anti-leukemia activity.
Cell Rep, 2023, 42(6):112547
bioRxiv, 2023, 10.1101/2023.03.17.533231
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.
Nat Commun, 2023, 10.1038/s41467-023-42930-y
Elife, 2021, 10e65654
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.
Mol Ther Oncolytics, 2022, 27:14-25
Cancer Res, 2018, 78(20):5731-5740
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
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.
Cell Rep, 2022, 39(12):110994
S7020 UNC0646 UNC0646 is a selective histone lysine methyltransferase (HMTase) inhibitor for G9a and GLP with IC50 of 6 nM and 15 nM , respectively, with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity.
E1163New MS177 MS177 is an EZH2-targeting PRTOAC degrader and a potent inhibitor of enzymatic EZH2, that effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukemia cell growth inhibition, apoptosis, and cell cycle progression arrest.
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.
S8918 MS1943 MS1943 is an orally bioavailable EZH2 selective degrader that effectively reduces EZH2 levels in cells with IC50 of 120 nM for inhibiting EZH2 methyltransferase activity.
E2911New UZH2 UZH2 is a potent and selective METTL3 inhibitor with an IC50 value of 5 nM in TR-FRET assay.
S8702 EBI-2511 EBI-2511 is a highly potent and orally active EZH2 inhibitor with an IC50 of 4 nM for EZH2(A667G).
S9659 UNC6852 UNC6852 is a selective degrader that targets polycomb repressive complex 2 (PRC2) with IC50 of 247 nM for EED. UNC6852 is based on PROTAC and contains an EED226-derived ligand and a ligand for VHL.
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.
Signal Transduct Target Ther, 2024, 9(1):2
Cell, 2023, 186(13):2765-2782.e28
Mol Cancer, 2023, 22(1):85
S7128 Tazemetostat (EPZ-6438) Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with Ki 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.
Signal Transduct Target Ther, 2024, 9(1):2
Nat Commun, 2024, 15(1):1367
Sci Rep, 2024, 14(1):4303
S7120 DZNeP (3-deazaneplanocin A) HCl DZNeP (3-deazaneplanocin A) HCl, an analog of adenosine, is a competitive inhibitor of S-adenosylhomocysteine hydrolase with Ki of 50 pM in a cell-free assay.
Mol Cancer, 2023, 22(1):85
Cell Stem Cell, 2023, 30(9):1235-1245.e6
Nat Commun, 2023, 14(1):4062
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.
J Immunother Cancer, 2023, 11(11)e007736
Clin Transl Med, 2023, 13(12):e1502
J Neuroinflammation, 2023, 20(1):168
S7062 Pinometostat (EPZ5676) Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with Ki 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.
Exp Hematol Oncol, 2023, 12(1):81
EMBO Rep, 2023, e56233.
Life Sci Alliance, 2023, 6(5)e202201619
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. BIX01294 also inhibits H3K36 methylation by oncoproteins NSD1, NSD2 and NSD3.
Dev Cell, 2023, 58(6):506-521.e5
Cell Death Dis, 2023, 14(9):627
Cell Death Dis, 2023, 14(9):627
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.
Cell Rep, 2023, 42(8):112885
Cell Rep, 2023, 42(6):112566
Int J Mol Sci, 2023, 24(11)9365
S7748 EPZ015666 (GSK3235025) EPZ015666 (GSK3235025) is a potent, selective and orally bioavailable PRMT5 inhibitor with Ki of 5 nM, >20,000-fold selectivity over other PMTs.
Nat Commun, 2023, 14(1):4003
Mol Cell, 2023, 83(15):2810-2828.e6
Cell Rep Med, 2023, 4(12):101326
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.
Acta Pharm Sin B, 2023, 13(6):2601-2612
J Exp Clin Cancer Res, 2023, 42(1):320
Pharmacol Res, 2022, 177:106122
S7004 EPZ005687 EPZ005687 is a potent and selective inhibitor of EZH2 with Ki of 24 nM in a cell-free assay, 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.
J Exp Clin Cancer Res, 2023, 42(1):320
BMC Med, 2022, 20(1):189
Cancers (Basel), 2022, 15(1)208
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).
Cancer Cell, 2023, 41(6):1118-1133.e12
Mol Ther, 2023, 10.1016/j.ymthe.2023.11.012
Clin Cancer Res, 2023, 29(1):271-278
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.
bioRxiv, 2024, 2024.02.06.579191
Cell Rep, 2023, 42(8):112885
Cell Rep, 2023, 42(6):112566
S8664 Pemrametostat (GSK3326595) Pemrametostat (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.
NPJ Precis Oncol, 2024, 8(1):52
Nat Metab, 2023, 10.1038/s42255-023-00861-4
Nat Metab, 2023, 5(9):1544-1562
S7265 MM-102 MM-102 (HMTase Inhibitor IX) is a high-affinity peptidomimetic inhibitor of the WDR5/MLL1 protein-protein interaction, which bind to WDR5 with Ki < 1 nM and IC50 =2.4nM.
Life Sci Alliance, 2023, 6(5)e202201619
Cell Stem Cell, 2022, S1934-5909(22)00417-9
Cell Rep, 2022, 39(7):110836
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.
Cell Rep, 2024, 43(2):113779
Cell Rep, 2023, 42(6):112566
Cancer Cell, 2022, 40(10):1190-1206.e9
S7805 EPZ011989 EPZ011989 is a potent, selective, orally bioavailable EZH2 inhibitor with Ki of <3 nM.
Cancers (Basel), 2024, 16(3):569.
Cancers (Basel), 2024, 16(3)569
Nat Cell Biol, 2023, 25(2):258-272
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.
Cell Rep, 2024, 43(1):113575
Cancers (Basel), 2023, 15(8)2199
bioRxiv, 2023, 2023.07.11.548643
S7570 UNC0379 UNC0379 is a selective, substrate competitive inhibitor of N-lysine methyltransferase SETD8 with IC50 of 7.3 μM, high selectivity over 15 other methyltransferases.
Cell Death Dis, 2023, 10.1038/s41419-023-06167-3
Cell Death Dis, 2023, 14(9):638
Cell Biosci, 2023, 13(1):107
S8111 GSK591 GSK591 (EPZ015866, GSK3203591) is a potent selective inhibitor of the arginine methyltransferase PRMT5 with IC50 of 4 nM.
Int J Mol Sci, 2023, 24(5)4327
Proc Natl Acad Sci U S A, 2022, 119(43):e2205255119
Hepatology, 2021, 10.1002/hep.32245
S8353 Lirametostat (CPI-1205) Lirametostat (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.
JCI Insight, 2022, e155899
Cancer Discov, 2021, candisc.0913.2020
Nat Commun, 2021, 12(1):6276
S7618 MI-2 (Menin-MLL Inhibitor) MI-2 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 446 nM.
Cell Stem Cell, 2022, S1934-5909(22)00417-9
Life Sci Alliance, 2022, 5(4)e202101187
J Immunol, 2021, ji1901348
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 Exp Clin Cancer Res, 2023, 42(1):96
Nat Commun, 2022, 13(1):6226
Nat Commun, 2022, 13(1):6226
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.
Nat Cell Biol, 2023, 25(2):258-272
J Clin Invest, 2023, 133(13)e169993
Breast Cancer Res, 2022, 24(1):52
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.
Sci Rep, 2024, 14(1):4303
Journal of Pharmacological Sciences, 2024, Pages 209-217
Nat Commun, 2023, 14(1):2806
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.
iScience, 2023, 26(3):106158
Cancer Res, 2022, 82(8):1534-1547
Sci Total Environ, 2022, 838(Pt 1):155713
S7804 GSK503 GSK503 is a potent and specific EZH2 methyltransferase inhibitor.
Int J Mol Sci, 2023, 24(10)8603
Cancer Res, 2022, CAN-22-0736
Front Genet, 2022, 13:1013475
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 Death Dis, 2023, 14(4):233
Oncogenesis, 2022, 11(1):45
Oncogene, 2021, 40(7):1375-1389
S7294 PFI-2 HCl PFI-2 is a potent, selective, and cell-active lysine methyltransferase SETD7 inhibitor with Ki (app) and IC50 of 0.33 nM and 2 nM, 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.
Life Sci Alliance, 2023, 6(5)e202201619
Pharmacol Res, 2022, 177:106122
Cell Rep, 2022, 39(12):110994
S7832 SGC707 SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3) with IC50 and Kd of 31 nM and 53 nM, respectively.
Cell Death Dis, 2022, 13(11):943
J Med Chem, 2020, 31
Transpl Int, 2020, 33(2):229-243
S7572 A-366 A-366 is a potent and selective G9a/GLP histone lysine methyltransferase inhibitor with IC50 of 3.3nM and 38nM, exhibiting >1000-fold selectivity for G9a/GLP over 21 other methyltransferases.
Cell Rep, 2024, 43(1):113575
Cancers (Basel), 2023, 15(8)2199
Cancer Cell, 2022, 40(10):1190-1206.e9
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.
Cell Death Differ, 2023, 10.1038/s41418-023-01167-4
Nat Biomed Eng, 2021, 10.1038/s41551-021-00718-9
J Med Chem, 2020, 31
S7619 MI-3 (Menin-MLL Inhibitor) MI-3 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 648 nM.
Nat Commun, 2023, 14(1):3062
Nature, 2021, 10.1038/s41586-021-04116-8
Clin Epigenetics, 2019, 11(1):137
S7591 BRD4770 BRD4770 is a histone methyltransferase G9a inhibitor with IC50 of 6.3 μM, and induces cell senescence.
Hum Cell, 2023, 10.1007/s13577-023-00924-4
Cell Insight, 2023, 2(4):100112
Pharmacol Res, 2022, 177:106122
S7575 LLY-507 LLY-507 is a cell-active, potent, and selective inhibitor of protein-lysine Methyltransferase SMYD2.
Pharmacol Res, 2022, 177:106122
Oncol Lett, 2020, 20(5):153
J Immunother Cancer, 2019, 7(1):277
S8624 Onametostat (JNJ-64619178) Onametostat (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.
Sci Rep, 2024, 14(1):4303
Nat Commun, 2023, 14(1):1078
J Immunother Cancer, 2023, 11(6)e006890
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.
Cancer Res, 2018, 78(20):5731-5740
Mol Cancer, 2017, 10.1186/s12943-016-0575-6
Virology, 2017, 506:34-44
S4021 Tolcapone Tolcapone (Ro 40-7592) is a selective, potent and reversible of catechol-O-methyl transferase (COMT) inhibitor with Ki of 30 nM.
FASEB J, 2022, 36(7):e22399
Viruses, 2021, 13(8)1533
Front Bioinform, 2021, 1:710591
S7820 EPZ020411 2HCl EPZ020411 is a potent and selective small molecule PRMT6 inhibitor with an IC50 of 10 nM.
Nat Commun, 2023, 14(1):1430
Inflamm Res, 2022, 71(3):309-320
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.
J Clin Invest, 2023, 133(13)e169993
iScience, 2023, 26(10):107726
Front Oncol, 2020, 10:524922
S8209 HLCL-61 HCL HLCL-61 hydrochloride is a potent and selective PRMT5 inhibitor for the treatment of acute myeloid leukemia.
Front Immunol, 2019, 10:174
Nat Commun, 2018, 9(1):1572
Cancer Res, 2018, 78(20):5731-5740
S8983 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.
PLoS Biol, 2023, 21(4):e3002038
Cell Death Dis, 2022, 13(2):155
JCI Insight, 2022, e155899
S7815 MI-136 MI-136 can specifically inhibit the menin-MLL interaction. It inhibits DHT-induced expression of androgen receptor (AR) target genes.
Breast Cancer Res, 2022, 24(1):52
Cancer Cell Int, 2022, 22(1):336
J Med Chem, 2020, 31
S3147 Entacapone Entacapone (OR-611) inhibits catechol-O-methyltransferase(COMT) with IC50 of 151 nM. Entacapone can be used for the research of Parkinson's disease. Entacapone serves as a inhibitor of FTO demethylation with an IC50 of 3.5 μM, can be used for the research of metabolic disorders.
Elife, 2022, 11e72668
bioRxiv, 2021, 10.1101/2021.03.22.436393
S8147 MS049 MS049 is a potent and selective inhibitor of PRMT4 and PRMT6 with IC50s of 34 nM and 43 nM, respectively.
Research Square, 2021, 10.21203/rs.3.rs-620216/v1
EMBO Rep, 2020, 21(2):e48597
S7868 SAH (S-Adenosyl-L-homocysteine) SAH (S-Adenosyl-L-homocysteine) is an inhibitor for (Methyltransferase Like 3-14) METTL3-METTL14 heterodimer complex (METTL3-14) with IC50 of 0.9 μM.
Clin Epigenetics, 2024, 16(1):18
Heliyon, 2023, 9(6):e16905
J Pept Sci, 2022, e3456.
S8934 VTP50469 VTP50469 is a potent, highly selective and orally active inhibitor of Menin-MLL interaction with Ki of 104 pM. VTP50469 exhibits anti-leukemia activity.
Cell Rep, 2023, 42(6):112547
bioRxiv, 2023, 10.1101/2023.03.17.533231
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.
Nat Commun, 2023, 10.1038/s41467-023-42930-y
Elife, 2021, 10e65654
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.
Mol Ther Oncolytics, 2022, 27:14-25
Cancer Res, 2018, 78(20):5731-5740
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
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.
Cell Rep, 2022, 39(12):110994
S7020 UNC0646 UNC0646 is a selective histone lysine methyltransferase (HMTase) inhibitor for G9a and GLP with IC50 of 6 nM and 15 nM , respectively, with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity.
E1163New MS177 MS177 is an EZH2-targeting PRTOAC degrader and a potent inhibitor of enzymatic EZH2, that effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukemia cell growth inhibition, apoptosis, and cell cycle progression arrest.
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.
S8918 MS1943 MS1943 is an orally bioavailable EZH2 selective degrader that effectively reduces EZH2 levels in cells with IC50 of 120 nM for inhibiting EZH2 methyltransferase activity.
E2911New UZH2 UZH2 is a potent and selective METTL3 inhibitor with an IC50 value of 5 nM in TR-FRET assay.
S8702 EBI-2511 EBI-2511 is a highly potent and orally active EZH2 inhibitor with an IC50 of 4 nM for EZH2(A667G).
S9659 UNC6852 UNC6852 is a selective degrader that targets polycomb repressive complex 2 (PRC2) with IC50 of 247 nM for EED. UNC6852 is based on PROTAC and contains an EED226-derived ligand and a ligand for VHL.
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.
J Clin Invest, 2023, 133(13)e169993
EBioMedicine, 2023, 92:104602
Cell Rep, 2023, 42(9):113145
S2184 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.
J Clin Invest, 2023, 133(13)e169993
Cell Rep, 2023, 42(9):113145
Biomed Pharmacother, 2022, 154:113663
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.
Leukemia, 2021, 10.1038/s41375-021-01121-8
Leukemia, 2021, 10.1038/s41375-021-01121-8
Int J Mol Sci, 2021, 22(2)E619
E1163New MS177 MS177 is an EZH2-targeting PRTOAC degrader and a potent inhibitor of enzymatic EZH2, that effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukemia cell growth inhibition, apoptosis, and cell cycle progression arrest.
E2911New UZH2 UZH2 is a potent and selective METTL3 inhibitor with an IC50 value of 5 nM in TR-FRET assay.

Choose Selective Histone Methyltransferase Inhibitors

Tags: Histone Methyltransferase inhibitor|Histone Methyltransferase agonist|Histone Methyltransferase activator|Histone Methyltransferase inducer|Histone Methyltransferase antagonist|Histone Methyltransferase signaling pathway|Histone Methyltransferase assay kit