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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SIRT2-IN-11

SIRT2-IN-11 (AEM1) is a selective SIRT2 inhibitor with an IC50 value of 18.5 μM. SIRT2-IN-11 p53-dependently induces apoptosis, activates expression of CDKN1A, PUMA and NOXA, and increases acetylation of p53. SIRT2-IN-11 can be used for the research of p53-related cancers[1].

  • CAS Number: 1005095-06-6
  • MF: C21H22N2O
  • MW: 318.4
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H10

PARP14 inhibitor H10, compound H 10, is a selective inhibitor against PARP14 (IC50=490 nM), over other PARPs (≈24 fold over PARP1). PARP14 inhibitor H10 induces caspase-3/7-mediated cell apoptosis[1].

  • CAS Number: 2084811-68-5
  • MF: C24H27N7O7S
  • MW: 557.58
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP7-IN-15

PARP7-IN-15 (Compound 18) is a PARP7 inhibitor with IC50 of 0.56 nM, that has antitumor activity[1].

  • CAS Number: 2819998-97-3
  • MF: C23H24F6N6O4
  • MW: 562.46
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TP 064

TP-064 is a potent, selective, and cell-active inhibitor of PRMT4 with IC50 of <10 nM and Kd of 7.1 nM, shows high selectivity (>100-fold) for PRMT4 over other PRMTs; reduces dimethylation of BAF155 (IC50=340±30 nM) and MED12 (IC50=43±10 nM) in a dose-dependent manner in cell-baed assays; inhibits the proliferation of a subset of multiple myeloma cell lines (NCI-H929, RPMI8226, Cell IC50 of 379 and 886 nM, respectively) with affected cells arrested in G1 phase of the cell cycle, but has no effect on acute myeloid leukemia, colon cancer, or lung cancer cell lines.

  • CAS Number: 2080306-20-1
  • MF: C28H34N4O2
  • MW: 458.595
  • Catalog: Histone Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 642.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.5±31.5 °C

UMB298

UMB298 is a potent and selective CBP/P300 bromodomain inhibitor[1].

  • CAS Number: 2266569-73-5
  • MF: C27H31ClN4O2
  • MW: 479.01
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-Methyl-5-azacytidine

6-Methyl-5-azacytidine is a potent DNMT inhibitor.

  • CAS Number: 105330-94-7
  • MF: C9H14N4O5
  • MW: 258.23
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dorsomorphin dihydrochloride

Dorsomorphin dihydrochloride (BML-275 dihydrochloride) is a potent, selective and ATP-competitive AMPK inhibitor, with a Ki of 109±16 nM.

  • CAS Number: 1219168-18-9
  • MF: C24H27Cl2N5O
  • MW: 472.410
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Agrimol B

Agrimol B is a polyphenol derived from Agrimonia pilosa Ledeb, suppresses adipogenesis via inducing SIRT1 translocation and expression, and reducing PPARγ expression[1].

  • CAS Number: 55576-66-4
  • MF: C37H46O12
  • MW: 682.754
  • Catalog: PPAR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 922.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 284.4±27.8 °C

Selaginellin

Selaginellin is an inhibitor of Reactive Oxygen Species and an activator of SIRT1. Selaginellin protects endothelial cells against homocysteine-induced senescence by inhibitng reactive oxygen species and upregulating SIRT1 gene expression[1].

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

SRTCX1003

SRTCX1003 is an orally active SIRT1 activator. SRTCX1003 suppresses inflammatory responses[1].

  • CAS Number: 1203480-86-7
  • MF: C23H23N5O3S
  • MW: 449.53
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxorubicin hydrochloride

Doxorubicin is a cytotoxic anthracycline antibiotic for the treatment of multiple cancers. The possible mechanisms by which doxorubicin acts in the cancer cell are intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair.

  • CAS Number: 23214-92-8
  • MF: C27H29NO11
  • MW: 543.52
  • Catalog: Bacterial
  • Density: 1.61 g/cm3
  • Boiling Point: N/A
  • Melting Point: 205ºC
  • Flash Point: 443.8ºC

HNHA

HNHA is a potent histone deacetylase (HDAC) inhibitor. HNHA arrests the cell cycle at the G1/S phase via p21 induction. HNHA inhibits tumor growth and tumor neovascularization. HNHA may be a potent anti-cancer agent against breast cancer[1].

  • CAS Number: 926908-04-5
  • MF: C17H21NO2S
  • MW: 303.42
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-4379

GDC-4379 is a JAK1 inhibitor that can be used for the research of asthma[1].

  • CAS Number: 2252277-73-7
  • MF: C21H18ClF2N7O3
  • MW: 489.86
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OICR 9429

OICR-9429 is a novel small-molecule antagonist of the Wdr5-MLL interaction with IC50 of 5 uM. inhibit proliferation and induce differentiation .target: Wdr5IC 50: 5 uMIn vitro: OICR-9429 inhibit proliferation and induce differentiation in p30-expressing human AML cells. OICR-9429 cause a significant decrease in viability in the majority of patient cells with mutations in the N-terminal part of the CEBPA gene. OICR-9429 displays exquisite cellular selectivity and specificity in disrupting critical protein-protein interactions between WDR5. [1] reduce the viability of primary human AML cells with N-terminal C/EBPα mutations by about 50% (mean value, n = 8) at 5 μM[2]In vivo:The reference for OICR-9429 to mice (female NOD-SCID) is 3 mg/kg.

  • CAS Number: 1801787-56-3
  • MF: C29H32F3N5O3
  • MW: 555.591
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 693.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.9±31.5 °C

Sirt2-IN-6

Sirt2-IN-6 (compound 24a) potent and selective inhibitor of SIRT2, with an IC50 of 0.815 μM. Sirt2-IN-6 can be used for the research of cancer[1].

  • CAS Number: 2243151-81-5
  • MF: C26H26N6O3S
  • MW: 502.59
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY-299

BAY-299 is a very potent, dual inhibitor with IC50s of 67 nM for BRPF2 bromodomains (BD), 8 nM for TAF1 BD2, and 106 nM for TAF1L BD2.

  • CAS Number: 2080306-23-4
  • MF: C25H23N3O4
  • MW: 429.468
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 688.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 370.3±31.5 °C

DTP3

DTP3 TFA is a potent and selective GADD45β/MKK7 inhibitor. DTP3 TFA targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway[1].

  • CAS Number: 1809784-29-9
  • MF: C26H35N7O5
  • MW: 525.600
  • Catalog: DNA/RNA Synthesis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAH-EZH2

SAH-EZH2 is an EZH2/EPP interaction inhibitor (Kd = 320 nM). SAH-EZH2 suppresses EZH2 expression and H3K27 trimethylation by PCR2 complex. SAH-EZH2 arrests proliferation and induces monocyte to macrophage differentiation of MLL-AF9 leukemia cell line.

  • CAS Number: 1453222-26-8
  • MF: C155H256N48O40
  • MW: 3432.05
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD3308

BRD3308 is a potent, selective HDAC3 inhibitor with IC50 of 54 nM, displays >20-fold selectivity over HDAC1 and HDAC2, >500-fold selectivity over other HDAC isoforms; attenuates PE-mediated phosphorylation of ERK, but not JNK; also activates HIV-1 transcription in the 2D10 cell line, induces outgrowth of HIV-1 from resting CD4+ T cells isolated from antiretroviral-treated, aviremic HIV+ patients ex vivo and disrupts HIV-1 latency; suppresses pancreatic β-cell apoptosis induced by inflammatory cytokines or glucolipotoxic stress, and increases functional insulin release.

  • CAS Number: 1550053-02-5
  • MF: C15H14FN3O2
  • MW: 287.289
  • Catalog: HIV
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 449.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.9±28.7 °C

ZEN-3219

ZEN-3219 is a BET inhibitor with IC50s of 0.48, 0.16 and 0.47 μM for BRD4(BD1), BRD4(BD2) and BRD4(BD1BD2), respectively. ZEN-3219 can be used to form PROTACs to induce degradation of BRD4[1].

  • CAS Number: 1952264-34-4
  • MF: C19H18N2O3
  • MW: 322.36
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BJE6-106

BJE6-106 (B106) is a potent, selective 3rd generation PKCδ inhibitor with an IC50 of 0.05 μM and targets selectivity over classical PKC isozyme PKCα (IC50=50 μM). BJE6-106 (B106) induces caspase-dependent apoptosis. BJE6-106 (B106) possesses tumor-specific effect.

  • CAS Number: 1564249-38-2
  • MF: C26H23NO2
  • MW: 381.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-27

JAK-IN-27 (compound 1) is an orally active and potent JAKS family kinase inhibitor with IC50s of 3.0 nM (TYK2), 7.7 nM (JAK1), 629.6 nM (JAK3), respectively. JAK-IN-27 inhibits IFN-α2B-induced phosphorylation of STAT3 in Jurkat cells (IC50=23.7 nM)[1].

  • CAS Number: 2673176-36-6
  • MF: C20H21F2N7O
  • MW: 413.42
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD4 Degrader-20

PROTAC BRD4 Degrader-20 (compound 195) is an bifunctional compound and an degrader of BRD4[1].

  • CAS Number: 2086300-61-8
  • MF: C55H58ClN9O7S2
  • MW: 1056.69
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fenoldopam hydrochloride

Fenoldopam (SKF 82526) hydrochloride is a D1 receptor agonist and a novel lysine-specific demethylase 1 (LSD1) inhibitor (IC50=0.8974 μM). Fenoldopam hydrochloride shows anti-hypertensive effects, anti-cancer cell proliferation activity and can induce cells apoptosis[1][2][3].

  • CAS Number: 181217-39-0
  • MF: C16H17Cl2NO3
  • MW: 342.22
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KDM5-C49

KDM5-C49 is a potent, selective KDM5 inhibitor with IC50 of 25, 30 and 59 nM for KDM5A, B and C, respectively; displays 25-100-fold selectivity over KDM6B, 2-30-fold selectivity over KDM4 family, but with less cell-permeablity.

  • CAS Number: 1596348-16-1
  • MF: C15H24N4O3
  • MW: 308.376
  • Catalog: Histone Demethylase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 531.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 275.0±30.1 °C

SGC-iMLLT

SGC-iMLLT is a potent and selective inhibitor of MLLT1/3-histone interactions, occupies the Kac/Kcr binding site of MLLT1 YD (ENL/YEATS1), with high binding activity at MLLT1 YD (IC50, 0.26 μM; Kd, 0.129 μM) and MLLT3 YD (AF9/YEATS3) (Kd, 0.077 μM)[1].

  • CAS Number: 2255338-25-9
  • MF: C22H24N6O
  • MW: 388.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BIX-01294

BIX-01294 is an inhibitor of G9a Histone Methyltransferase with IC50 of 1.9 μM.

  • CAS Number: 935693-62-2
  • MF: C28H38N6O2
  • MW: 490.64
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 178.44° C
  • Flash Point: N/A

TGP-377/421

TGP-377/421 (Targapre-miR-377/421) is a smalll molecule targets pre-miR-377 and inhibits its processing, binds to miR-377's Dicer processing site with Kd of 29 uM.TGP-377/421 inhibits the cellular biogenesis of miR-377 in HUVECs, reduced mature miR-377 levels in a dose-dependent fashion with IC50 of 5 uM, also inhibits miR-421.

  • CAS Number: 16752-89-9
  • MF: C20H16N6
  • MW: 340.39
  • Catalog: MicroRNA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHR0302

SHR0302 is a potent and orally active all members of the JAK family inhibitor, particularly JAK1. The selectivity of SHR0302 for JAK1 is >10-fold for JAK2, 77-fold for JAK3, 420-fold for Tyk2. SHR0302 inhibits JAK1-STAT3 phosphorylation and induces the apoptosis of hepatic stellate cells. SHR0302 has anti-proliferative and anti-inflammatory effects[1][2].

  • CAS Number: 1445987-21-2
  • MF: C18H22N8O2S
  • MW: 414.48
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(3-Chlorophenyl)-3-(1-oxo-4-phenylphthalazin-2(1H)-yl)propanamide

PARP1-IN-8 (compound 11c) is a potent and BBB-penetrated PARP1 inhibitor, with an IC50 of 97 nM. PARP1-IN-8 shows significantly potent anti-proliferative activity against Human lung adenocarcinoma epithelial cell line A549[1].

  • CAS Number: 836640-15-4
  • MF: C23H18ClN3O2
  • MW: 403.86
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A