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.


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SRT 2104

SRT 2104 is a brain-permeable activator of SIRT1, used for the research of type 2 diabetes mellitus and Huntington's disease.

  • CAS Number: 1093403-33-8
  • MF: C26H24N6O2S2
  • MW: 516.638
  • Catalog: Sirtuin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RBN-2397

RBN-2397 is a potent, accross species and orally active NAD+ competitive inhibitor of PARP7 (IC50<3 nM). RBN-2397 selectively binds to PARP7 (Kd=0.001 μM) and restores interferon (Type I) signaling. RBN-2397 has the potential for the study of advanced or metastatic solid tumors[1][2].

  • CAS Number: 2381037-82-5
  • MF: C20H23F6N7O3
  • MW: 523.43
  • Catalog: PARP
  • Density: 1.53±0.1 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MM-401 TFA

MM-401 (TFA) is a MLL1 H3K4 methyltransferase inhibitor. MM-401 inhibits MLL1 activity (IC50 = 0.32 µM) by blocking MLL1-WDR5 interaction. MM-401 can induce cell cycle arrest, Apoptosis and differentiation. MM-401 can be used for the research of MLL leukemia[1].

  • CAS Number: 1442106-11-7
  • MF: C31H47F3N8O7
  • MW: 700.75
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azuleno[6,5-b]furan-2,5-dione,4-(acetyloxy)-3,3a,4,4a,7a,8,9,9a-octahydro-4a,8-dimethyl-3-methylene-,(3aR,4S,4aR,7aR,8R,9aR)-

Helenalin acetate, a natural NF-κB inhibitor, is a potent C/EBPβ inhibitor. Helenalin acetate has anti-inflammatory and anticancer activities[1].

  • CAS Number: 10180-86-6
  • MF: C17H20O5
  • MW: 304.33800
  • Catalog: Histone Demethylase
  • Density: 1.22g/cm3
  • Boiling Point: 466.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 207.1ºC

PRMT5-IN-11

PRMT5-IN-11 is a promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range.

  • CAS Number: 2567564-33-2
  • MF: C13H17N5O4
  • MW: 307.31
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Calphostin C

Calphostin C is a potent and specific inhibitor of protein kinase C. Calphostin C is an antitumor antibiotic. Calphostin C has 1000 times more inhibitory to protein kinase C with an IC50 of 0.05 μM than other protein kinases. Calphostin C induces apoptosis in some tumor cell lines. Calphostin C has potent cytotoxic activity and antitumor activity[1].

  • CAS Number: 121263-19-2
  • MF: C44H38O14
  • MW: 790.764
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1039.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 317.0±27.8 °C

Procyanidin B3

Procyanidin B3 is a natural product, acts as a specific HAT inhibitor, binds to the other site of p300 instead of the active site, selectively inhibits p300-mediated androgen receptor acetylation. Procyanidin B3 has no effect on HDAC or HMT (histone methyltransferase)[1].

  • CAS Number: 23567-23-9
  • MF: C30H26O12
  • MW: 578.520
  • Catalog: Histone Acetyltransferase
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 955.3±65.0 °C at 760 mmHg
  • Melting Point: 218-219℃
  • Flash Point: 531.6±34.3 °C

UNC0646

UNC0646 is a potent and selective G9a inhibitor with IC50 of 6 nM.IC50 value: 6 nM [1]Target: G9aUNC0646 is a potent and selective inhibitor of the homologous protein lysine methyltransferases, G9a and GLP (IC50 values are 6 nM and 15 nM for G9a and GLP, respectively). UNC0646 potently blocks G9a/GLP methyltransferase activity in cells (IC50 = 10 nM in MCF7 cells); exhibits low cellular toxicity (EC50 = 4.7 μM in MCF7 cells). UNC0646 is selective for G9a/GLP over a range of other protein lysine methyltransferases and protein arginine methyltransferases.

  • CAS Number: 1320288-17-2
  • MF: C36H59N7O2
  • MW: 621.899
  • Catalog: Histone Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 754.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 410.1±35.7 °C

Histone Acetyltransferase Inhibitor II

Histone Acetyltransferase Inhibitor II is a potent and cell permeable p300 inhibitor, with an IC50 of 5 µM; Histone Acetyltransferase Inhibitor II can be used in cancer research.

  • CAS Number: 932749-62-7
  • MF: C20H16Br2O3
  • MW: 464.14700
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5WKS

G9a-IN-1 (Compound 113) is a G9a protein inhibitor. G9A/EHMT2 is a nuclear histone lysine methyltransferase that catalyzes histone H3 lysine 9 dimethylation (H3K9me2), which is a reversible modification generally associated with transcriptional gene silencing. G9a-IN-1 can be used for the research of autoimmune disorders or cancer[1].

  • CAS Number: 1350752-07-6
  • MF: C24H36ClN5O2
  • MW: 462.028
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 529.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.9±30.1 °C

dBRD4-BD1

dBRD4-BD1 is a selective and durable BRD4 degrader with an DC50 value of 280 nM (Dmax=77%). dBRD4-BD1 upregulates BRD2/3 protein level and shows low cytotoxicity than iBRD4-BD1[1].

  • CAS Number: 2839318-19-1
  • MF: C50H53F3N8O9
  • MW: 967.00
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF 06409577

PF-06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC50 of 7 nM.

  • CAS Number: 1467057-23-3
  • MF: C19H16ClNO3
  • MW: 341.78800
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Crebinostat

Crebinostat is a potent histone deacetylase (HDAC) inhibitor with IC50 values of 0.7 nM, 1.0 nM, 2.0 nM and 9.3 nM for HDAC1, HDAC2, HDAC3 and HDAC6, respectively. Crebinostat potently induces acetylation of both histone H3 and histone H4 as well as enhances the expression of the cAMP response element-binding protein (CREB) target gene Egr1. Crebinostat increases the density of synapsin-1 punctae along dendrites in cultured neurons. Crebinostat can modulate chromatin-mediated neuroplasticity and exhibits enhanced memory in mice[1].

  • CAS Number: 1092061-61-4
  • MF: C20H23N3O3
  • MW: 353.415
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3-IN-14

JAK3-IN-14 (compound 1) is a potent JAK3 inhibitor, with IC50 values of 38 and 600 nM for JAK3 and JAK2, respectively. JAK3-IN-14 shows inhibitory of IL-4 and IL-3 induced TF-1 cell proliferation, with IC50 values of 600 and 500 nM, respectively[1].

  • CAS Number: 454234-24-3
  • MF: C18H13N3O
  • MW: 287.32
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS-402

MS402 is a BD1-selective BET BrD inhibitor with Kis of 77 nM, 718 nM, 110 nM, 200 nM, 83 nM, and 240 nM for BRD4(BD1), BRD4(BD2), BRD3(BD1), BRD3(BD2), BRD2(BD1) and BRD2(BD2), respectively. MS402 blocks Th17 cell differentiation and ameliorates colitis in mice[1].

  • CAS Number: 1672684-68-2
  • MF: C20H19ClN2O3
  • MW: 370.83
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SGC 0946

SGC0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM; selectively kill mixed lineage leukaemia cells.IC50 value: 0.3 nM(DOT1L) [1]Target: selective DOT1L inhibitorSGC 0946 is over 100-fold selective for other histone methyltransferases/HMTs. SGC 0946 potently reduces H3K79 dimethylation with IC50 of 2.6 nM in A431 cells, and 8.8 nM in MCF10A cells, which potently and selectively kills cells containing an MLL translocation. SGC 0946 is much more potent than its close analog EPZ004777, and serves as an excellent chemical probe for investigating DOT1L and further development of DOT1L inhibitors for cancer therapy.

  • CAS Number: 1561178-17-3
  • MF: C28H40BrN7O4
  • MW: 618.566
  • Catalog: Histone Methyltransferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 771.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 420.4±32.9 °C

BRD4 Inhibitor-27

BRD4 Inhibitor-27 (compound 6) is a BRD4 inhibitor with IC50 of 9.6 and 11.3 μM for BRD4 BD1 and BRD4 BD2, respectively. BRD4 Inhibitor-27 has the potential to study cancer[1].

  • CAS Number: 930039-92-2
  • MF: C16H13F3N6
  • MW: 346.31
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubacin

Tubacin is a potent and selective inhibitor of HDAC6, with an IC50 value of 4 nM and approximately 350-fold selectivity over HDAC1.

  • CAS Number: 537049-40-4
  • MF: C41H43N3O7S
  • MW: 721.861
  • Catalog: HDAC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3,4-Dimethoxy-N-(5-methylisoxazol-3-yl)benzamide

BRD4 Inhibitor-24 (compound 3U) is a potent BRD4 inhibitor, BRD4 Inhibitor-24 shows antitumor activity against MCF7 and K652 cells, with IC50 values of 33.7 and 45.9 μM, respectively (extracted from patent CN107721975A)[1].

  • CAS Number: 309951-18-6
  • MF: C13H14N2O4
  • MW: 262.26
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKC β pseudosubstrate

PKC β pseudosubstrate is a selective cell-permeable inhibitor of PKC[1].

  • CAS Number: 172308-76-8
  • MF: C177H294N62O38S3
  • MW: 3994.82
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Glucose-conjugated MGMT inhibitor

Glucose-conjugated MGMT inhibitor is a potent O6-methylguanine-DNAmethyl-transferase (MGMT) inhibitor, with IC50s of 32 nM in vitro (cell extracts) and 10 nM in HeLa S3 cells.

  • CAS Number: 382607-78-5
  • MF: C24H34BrN5O7S
  • MW: 616.52500
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP-1/2-IN-1

PARP-1/2-IN-1 is a potent PARP-1/2 inhibitor with IC50 of 0.51 nM and 23.11 nM, respectively.

  • CAS Number: 1903744-45-5
  • MF: C24H27FN4O3
  • MW: 438.49
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EZH2-IN-8

EZH2-IN-8 is a potent inhibitor of EZH2. EZH2 overexpression or mutations in the SET region (Y641F, Y641N, A687V, A677G point mutations) all lead to abnormal elevation of H3K27me3 and promote the growth and development of many types of tumors, such as breast cancer, prostate cancer, leukemia, etc. EZH2-IN-8 has the potential for the research of cancer diseases (extracted from patent WO2021129629A1, compound 265)[1].

  • CAS Number: 2659225-08-6
  • MF: C31H40F2N4O2S
  • MW: 570.74
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Naphthol AS-E

Naphthol AS-E is a potent and cell-permeable inhibitor of KIX-KID interaction. Naphthol AS-E directly binds to the KIX domain of CBP (Kd:8.6 µM), blocks the interaction between the KIX domain and the KID domain of CREB with IC50 of 2.26 µM. Naphthol AS-E can be used for cancer research.

  • CAS Number: 92-78-4
  • MF: C17H12ClNO2
  • MW: 297.73600
  • Catalog: Epigenetic Reader Domain
  • Density: 1.399 g/cm3
  • Boiling Point: 416.5ºC at 760 mmHg
  • Melting Point: 255°C
  • Flash Point: 205.7ºC

Menin-MLL inhibitor 26

Menin-MLL inhibitor 26 is a Menin-MLL inhibitor. Menin-MLL inhibitor 26 also is an active reference. Menin-MLL inhibitor 26 can inhibits cell growth. Menin-MLL inhibitor 26 can be used for the research of leukemia[1].

  • CAS Number: 2440018-29-9
  • MF: C27H29F3N6O3S
  • MW: 574.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Propen-1-one,1-(4-methoxyphenyl)-3-phenyl-

4'-Methoxychalcone regulates adipocyte differentiation through PPARγ activation. 4'-Methoxychalcone modulates the expression and secretion of various adipokines in adipose tissue that are involved in insulin sensitivity[1].

  • CAS Number: 959-23-9
  • MF: C16H14O2
  • MW: 238.28100
  • Catalog: PARP
  • Density: 1.114g/cm3
  • Boiling Point: 397.5ºC at 760mmHg
  • Melting Point: 101-103 °C(lit.)
  • Flash Point: 180.5ºC

PFI 4

PFI-4 is a potent and selective and cell permeable BRPF1 bromodomain inhibitor (IC50 = 80 nM). Exhibits >100-fold selectivity for BRPF1 over a panel of other bromodomains including BRPF2 (BRD1), BRPF3 and BRD4. IC50 value: 80 nMTarget: BRPF1in vitro: Disrupts BRPF1 binding to histone H3.3. PFI-4 is a chemical probe that specifically binds to the bromodomain of BRPF1 with a Kd =13 nM as determined by ITC. It reduces recovery time in triple BRD cell construct in FRAP, inhibiting binding to tri-acetylated histone 4 (residues 1-21). It has much lower affinity for bromodomain 1 of BRD4 (Kd = >50 μM) and is selective for BRPF1 over BRPF2 and BRPF3. PFI-4 is potent in cells, with an IC50 value of 250 nM.

  • CAS Number: 900305-37-5
  • MF: C21H24N4O3
  • MW: 380.440
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 512.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.5±30.1 °C

CBL0137

CBL0137, a curaxin compound, is a histone chaperone facilitates chromatin transcription (FACT) inhibitor. CBL0137 downregulates NF-?B and activates p53. CBL0137 restores both histone H3 acetylation and trimethylation. CBL0137 is an anticancer agent. CBL0137 induces cancer cell apoptosis[1].

  • CAS Number: 1197996-80-7
  • MF: C21H24N2O2
  • MW: 336.43
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-18

JAK-IN-18 is a potent inhibitor of JAK. JAK-IN-18 is useful for the research of multiple diseases, particularly ocular, skin, and respiratory diseases (extracted from patent WO2018204238A1, compound 1)[1].

  • CAS Number: 2247925-32-0
  • MF: C27H28F2N6O3
  • MW: 522.55
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dc-s239

DC-S239 is a selective histone methyltransferase SET7 inhibitor with an IC50 value of 4.59 μM. DC-S239 also displays selectivity for DNMT1, DOT1L, EZH2, NSD1, SETD8 and G9a. DC-S239 has anticancer activity[1].

  • CAS Number: 303141-21-1
  • MF: C15H15N3O5S
  • MW: 349.36
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A