Epigeneics include any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells. Many types of epigenetic processes have been identified—they include DNA methylation, alteration in the structure of histone proteins and gene regulation by small noncoding microRNAs.

Many different DNA and histone modifications have been identified to determine the epigenetic landscape. DNA methylation is mainly mediated by DNA-methyl transferase (DNMT), there are two known types of DNMT, namely DNMT1, which preserves preexisting pattern of methylation after cell replication, and DNMT3A/B, so-called “de novo” DNMT, which methylate previously unmethylated DNA. Histone modifications mainly include acetylation, methylation, phosphorylation, and ubiquitination. The acetylation of histones can be mediated by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), while Histhone demethylation is performed by two classes of histone demethylases: lysine-specific demethylase (LSD) family proteins (LSD1 and LSD2) and JmjC domaincontaining histone demethylase (JHDM). Furthermore, enzymes involved in epigenetic modifications can also be governed by miRNAs. For example, miR-34a can directly inhibit the activities of SIRT1 to regulate cholesterol homeostasis.

The accumulated evidence indicates that many genes, diseases, and environmental substances are part of the epigenetics picture. At the FDA, scientists are investigating many drugs that function through epigenetic mechanisms. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors can also work alone or in combination with other therapeutic agents.

References:
[1] Bob Weinhold. Environ Health Perspect. 2006 Mar; 114(3): A160–A167.
[2] Xu W, et al. Genet Epigenet. 2016 Sep 25;8:43-51.
[3] Biswas S, et al. Pharmacol Ther. 2017. doi: 10.1016/j.pharmthera.2017.02.011.
[4] Perri F, et al. Crit Rev Oncol Hematol. 2017 Mar;111:166-172.


Anti-infection >
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Vafidemstat

Vafidemstat is a dual lysine-specific histone demethylase (LSD1)/MAO-B inhibitor.

  • CAS Number: 1357362-02-7
  • MF: C19H20N4O2
  • MW: 336.39
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TYA-018

TYA-018 is an orally active, potent and highly selective HDAC6 inhibitor. TYA-018 can protect heart function in mice. TYA-018 also enhances energetics in mice by increasing expression of targets associated with fatty acid metabolism, protein metabolism, and oxidative phosphorylation[1].

  • CAS Number: 2653254-31-8
  • MF: C15H13ClF2N4O3S2
  • MW: 434.87
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK3368715

GSK3368715 (EPZ019997) is an orally active, reversible, and S-adenosyl-L-methionine (SAM) uncompetitive type I protein arginine methyltransferases (PRMTs) inhibitor (IC50=3.1 nM (PRMT1), 48 nM (PRMT3), 1148 nM (PRMT4), 5.7 nM (PRMT6), 1.7 nM (PRMT8)). GSK3368715 (EPZ019997) produces a shift in arginine methylation states, alters exon usage, and has strong anti-cancer activity[1].

  • CAS Number: 1629013-22-4
  • MF: C20H38N4O2
  • MW: 366.54
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-63

HDAC-IN-63 (Compound 63) is a dual FLT3/HDAC inhibitor (IC50: 0.844 and 30.0 nM for FLT3 and HDAC1 respectively). HDAC-IN-63 inhibits MV4-11 cell proliferation (IC50: 92 nM. HDAC-IN-63 induces apoptosis and arrests cell cycle in MV4-11 cells. HDAC-IN-63 can be used for research of acute myeloid leukemia (AML)[1].

  • CAS Number: 2920046-95-1
  • MF: C25H26Cl2N6O3
  • MW: 529.42
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DC-05

DC-05 is a DNA methyltransferase 1 (DNMT1) inhibitor, with an IC50 and a Kd of 10.3 μM and 1.09 μM, respectively.

  • CAS Number: 890643-16-0
  • MF: C25H25N3O
  • MW: 383.486
  • Catalog: DNA Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 667.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.5±31.5 °C

Tefinostat

Tefinostat (CHR-2845) is a monocyte/macrophage-targeted pan HDAC inhibitor, cleaved into active acid CHR-2847 by the intracellular esterase human carboxylesterase-1 (hCE-1). Anti-monocytoid lineage leukaemias activity[1].

  • CAS Number: 914382-60-8
  • MF: C28H37N3O5
  • MW: 495.61000
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ro-318220

Ro 31-8220 mesylate is a potent PKC inhibitor, with IC50s of 5, 24, 14, 27, 24 and 23 nM for PKCα, PKCβI, PKCβII, PKCγ, PKCε and rat brain PKC, respectively. Ro 31-8220 also significantly inhibits MAPKAP-K1b, MSK1, S6K1 and GSK3β

  • CAS Number: 138489-18-6
  • MF: C26H27N5O5S2
  • MW: 553.65
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK8814

GSK8814 is a potent, selective, and ATAD2/2B bromodomain chemical probe and inhibitor, with a binding constant pKd=8.1 and a pKi=8.9 in BROMOscan. GSK8814 binds to ATAD2 and BRD4 BD1 with pIC50s of 7.3 and 4.6, respectively. GSK8814 shows 500-fold selectivity for ATAD2 over BRD4 BD1[1].

  • CAS Number: 1997369-78-4
  • MF: C28H35F2N5O3
  • MW: 527.61
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-12

PRMT5-IN-12 shows remarkable inhibitory activity on PRMT5.

  • CAS Number: 2568927-94-4
  • MF: C32H40N4O4
  • MW: 544.68
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

B2

SIRT2-IN-8 is a potent SIRT2 inhibitor. SIRT2-IN-8 can be used for Huntington’s and Parkinson’s diseases research[1].

  • CAS Number: 115687-05-3
  • MF: C20H17ClN4O3
  • MW: 396.83
  • Catalog: Sirtuin
  • Density: 1.4±0.1g/cm3
  • Boiling Point: 645.5±55.0°C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.2±31.5°C

OARV-771

OARV-771 is a VHL-based BET degrader (PROTAC) with improved cell permeability. OARV-771 shows DC50s of 6, 1, and 4 nM for Brd4, Brd2 and Brd3, respectively[1].

  • CAS Number: 2683008-37-7
  • MF: C49H59ClN8O8S2
  • MW: 987.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VinSpinIn

VinSpinIn is a Spindlin1 inhibitor (KD: 9.9 nM for SPIN149-262). VinSpinIn is a chemical probe for tudor domain of Spindlin1. VinSpinIn can be used to study chromatin function[1].

  • CAS Number: 2380021-98-5
  • MF: C42H58N8O4
  • MW: 738.96
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JQ-1 carboxylic acid

JQ-1 carboxylic acid is a highly potent, selective and cell-permeable BRD4 inhibitor with IC50s of 77 nM and 33 nM for BRD4(1) and BRD4(2), respectively.

  • CAS Number: 202592-23-2
  • MF: C19H17ClN4O2S
  • MW: 400.882
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 661.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.9±34.3 °C

5,7-Dihydroxychromone

5,7-Dihydroxychromone, the extract of Cudrania tricuspidata, activates Nrf2/ARE signal and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis. 5,7-Dihydroxychromone inhibits the expression of activated caspase-3 and caspase-9 and cleaved PARP in 6-OHDA-induced SH-SY5Y cells[1].

  • CAS Number: 31721-94-5
  • MF: C9H6O4
  • MW: 178.141
  • Catalog: Arenavirus
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 399.4±42.0 °C at 760 mmHg
  • Melting Point: 232-273℃
  • Flash Point: 170.8±21.4 °C

BI-9321 trihydrochloride

BI-9321 trihydrochloride is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 trihydrochloride is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 trihydrochloride specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].

  • CAS Number: 2387510-87-2
  • MF: C22H24Cl3FN4
  • MW: 469.81
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RFARKGALRQKNVHEVKN

Protein Kinase C (19-36) is a pseudosubstrate peptide inhibitor of protein kinase C (PKC), with an IC50 of 0.18 μM. Protein Kinase C (19-36) markedly attenuated vascular hyperproliferation and hypertrophy as well as glucose-induced suppression of natriuretic peptide receptor response[1].

  • CAS Number: 113731-96-7
  • MF: C93H159N35O24
  • MW: 2151.48
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSD1 inhibitor BT5

NSD1 inhibitor BT5 is a covalent, small molecule inhibitor of NSD1 histone methyltransferase with IC50 of 1.4 uM, shows no covalent binding to NSD2.

  • CAS Number: 2351225-46-0
  • MF: C10H11N3Os
  • MW: 221.278
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Psychosine-d7

Psychosine-d7 is deuterium labeled Psychosine. Psychosine, a substrate of the galactocerebrosidase (GALC) enzyme, is a potential biomarker for Krabbe disease. Psychosine is a highly cytotoxic lipid, capable of inducing cell death in a wide variety of cell

  • CAS Number: 2315262-31-6
  • MF: C24H40D7NO7
  • MW: 468.68
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MI-3454

MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC50 of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia through downregulation of key genes involved in leukemogenesis[1].

  • CAS Number: 2134169-43-8
  • MF: C32H35F3N8OS
  • MW: 636.73
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurora Kinase Inhibitor II

Aurora kinase inhibitor-2 is a selective and ATP-competitive Aurora kinase inhibitor with IC50s of 310 nM and 240 nM for Aurora A and Aurora B, respectively[1].

  • CAS Number: 331770-21-9
  • MF: C23H20N4O3
  • MW: 400.43000
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SW155246

SW155246 is a DNA methyltransferase (DNMT1) selective inhibitor with IC50s of 1.2 and 38 μM for hDNMT1 and mDNMT3A, respectively. SW155246 can be used for the research of cancer and other diseases[1].

  • CAS Number: 420092-79-1
  • MF: C16H11ClN2O5S
  • MW: 378.787
  • Catalog: DNA Methyltransferase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 613.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 324.6±34.3 °C

JG-2016

JG-2016 is a potent inhibitor of histone acetyltransferase 1 (HAT1), with an IC50 of 14.8 μM in the HAT1 acetylation assays[1].

  • CAS Number: 2887480-87-5
  • MF: C18H21ClN4O3
  • MW: 376.84
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZEN-3694

ZEN-3694 is a bromo-structural domain extra-terminal inhibitor (BETi) with activity in androgen signaling inhibitor (ASI) resistance models and can be used in combination with enzalutamide to study metastatic desmoplasia-resistant prostate cancer.

  • CAS Number: 1643947-30-1
  • MF: C19H19N5O
  • MW: 333.39
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZLD 1039

ZLD1039 is an inhibitor of enhancer of zeste homolog 2 (EZH2; IC50 = 5.6 nM).

  • CAS Number: 1826865-46-6
  • MF: C36H48N6O3
  • MW: 612.8
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP/p300-IN-21

CBP/p300-IN-21 (Compound 5d) is a selective CBP/p300 inhibitor (IC50: 0.07 and 1.755 μM for p300 and CBP). CBP/p300-IN-21 decreases H3K18Ac level. CBP/p300-IN-21 inhibits growth of 4T1 tumor growth in mice[1].

  • CAS Number: 1065581-69-2
  • MF: C19H16ClNO4
  • MW: 357.79
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY 1238097

BAY1238097 is a potent and selective inhibitor of BET binding to histones and has strong anti-proliferative activity in different AML (acute myeloid leukemia) and MM (multiple myeloma) models through down-regulation of c-Myc levels and its downstream transcriptome (IC50 <100 nM in a TR-FRET assay).

  • CAS Number: 1564268-08-1
  • MF: C25H33N5O3
  • MW: 451.56
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Decapeptide-12

Decapeptide-12, a small oligopeptide, is a tyrosinase inhibitor that interacts with C-terminal residue of tyrosinase (Kd: 61.1 μM). Decapeptide-12 is a competitive inhibitor of mushroom tyrosinase (IC50: 40 µM). Decapeptide-12 also increases transcription of SIRT. Decapeptide-12 reduces melanin content in melanocytes. Decapeptide-12 is used for the research of melanogenesis, senescence, inflammation [1][2][3].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-J1

GSK-J1 is a potent inhibitor of H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A, with IC50 of 60 nM towards KDM6B. 

  • CAS Number: 1373422-53-7
  • MF: C22H23N5O2
  • MW: 389.450
  • Catalog: Histone Demethylase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 608.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 322.0±31.5 °C

CD235

CD235, is a structurally similar analogue of CD161 (a potent and orally bioavailable BET bromodomain inhibitor)[1].

  • CAS Number: 1627716-57-7
  • MF: C26H20FN5O2
  • MW: 453.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tazemetostat hydrobromide

Tazemetostat hydrobromide (EPZ-6438 hydrobromide) is a potent, selective and orally available EZH2 inhibitor. Tazemetostat hydrobromide inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 with a Ki value of 2.5 nM. Tazemetostat hydrobromide inhibits EZH2 with IC50s of 11 and 16 nM in peptide assay and nucleosome assay, respectively. Tazemetostat hydrobromide inhibits Rat EZH2 with an IC50 of 4 nM. Tazemetostat hydrobromide also inhibits EZH1 with an IC50 of 392 nM.

  • CAS Number: 1467052-75-0
  • MF: C34H45BrN4O4
  • MW: 653.65
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A