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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NSD3-IN-3

NSD3-IN-3 is a potent NSD3 inhibtor with an IC50 value of 1.86 μM. NSD3-IN-3 has anticancer activity and significantly inhibits the growth and proliferation of non-small cell lung cancer cell line H460[1].

  • CAS Number: 445416-12-6
  • MF: C15H17N5O2S
  • MW: 331.39
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZL0420

ZL0420 is a potent, highly selective BRD4 inhibitor with IC50 of 27 and 32 nM for BRD4-BD1 and BRD4-BD2, respectively; displays selectivity over BRD2, BRD3, and BRDT (BRD2-BD1 and BRD2-BD2, IC50=803 and 1736 nM); disrupts the BRD4 complex with Pol II and histones, inhibits poly(I:C)-induced expression of innate immune genes IL6 and CIG5 in human small airway epithelial cells (hSAECs) (IC50=0.54 and 0.51 uM); blocks Poly(I:C)-induced inflammation and neutrophilia in vivo.

  • CAS Number: 2229039-45-4
  • MF: C16H16N4O2
  • MW: 296.324
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 645.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.4±31.5 °C

EPZ028862

EPZ028862 is a selective SMYD3 inhibitor for cancer research[1].

  • CAS Number: 1887082-53-2
  • MF: C20H30N4O4S
  • MW: 422.54
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC CBP/P300 Degrader-1

PROTAC CBP/P300 Degrader-1 is a potent PROTAC CBP/P300 degrader. PROTAC CBP/P300 Degrader-1 potently inhibited cell viability of multiple cancer cell lines[1].

  • CAS Number: 2484739-48-0
  • MF: C46H53F2N11O6
  • MW: 893.98
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Upadacitinib

Upadacitinib (ABT-494) is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM, being developed for the treatment of several autoimmune disorders.

  • CAS Number: 1310726-60-3
  • MF: C17H19F3N6O
  • MW: 380.368
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Spisulosine-d3

Spisulosine-d3 is deuterium labeled Spisulosine. Spisulosine (ES-285) is an antiproliferative (antitumoral) compound of marine origin. Spisulosine inhibits the growth of the prostate PC-3 and LNCaP cells through intracellular ceramide accumulation and PKC

  • CAS Number: 1246298-31-6
  • MF: C18H36D3NO
  • MW: 288.53
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MDL-801

MDL-801 is an activator of SIRT6 deacetylation, with an EC50 value of 5.7 µM[1].

  • CAS Number: 2275619-55-9
  • MF: C20H14BrCl2FN2O6S2
  • MW: 612.27
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4 Inhibitor-19

BRD4 Inhibitor-19 is a BET inhibitor with an IC50 of 55 nM for BRD4-BD1. BRD4 Inhibitor-19 can be used for multiple myeloma research[1].

  • CAS Number: 2757865-63-5
  • MF: C29H25N5O3
  • MW: 491.54
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK121 (trifluoroacetate salt)

GSK-121 Trifluoroacetates a selective PAD4 inhibitor[1].

  • CAS Number: 1652591-80-4
  • MF: C25H26F3N5O3
  • MW: 501.501
  • Catalog: Cancer
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Derrone

Derrone, a prenylated isoflavones, is an Aurora kinase inhibitor, with IC50 values of 6 and 22.3 μM against Aurora B and Aurora A, respectively. Derrone shows anti-tumor activity[1][2].

  • CAS Number: 76166-59-1
  • MF: C20H16O5
  • MW: 336.34
  • Catalog: Aurora Kinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 584.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.6±23.6 °C

Benzyl selenocyanate

Benzyl selenocyanate is a chemopreventive agent for various chemically induced tumors in animal models at both the initiation and postinitiation stages. Benzyl selenocyanate is an inhibitor of DNA (cytosine-5)-methyltransferase (Mtase), with an with an IC50 of 8.4 µM[1].

  • CAS Number: 4671-93-6
  • MF: C8H7NSe
  • MW: 196.10800
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: 276.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 121.2ºC

GSK-J4 Hydrochloride

GSK-J4 hydrochloride is a potent dual inhibitor of H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A with IC50s of 8.6 and 6.6 μM, respectively. GSK-J4 hydrochloride inhibits LPS-induced TNF-α production in human primary macrophages with an IC50 of 9 μM. GSK-J4 hydrochloride is a cell permeable prodrug of GSK-J1[1][2][3].

  • CAS Number: 1797983-09-5
  • MF: C24H28ClN5O2
  • MW: 453.964
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABBV-712

ABBV-712 is a selective inhibitor of Tyrosine kinase 2 (TYK2), with IC50 of 0.195 μM, that play important role in autoimmune diseases[1].

  • CAS Number: 2368945-27-9
  • MF: C24H28N4O5
  • MW: 452.50
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JGB1741

JGB1741 (ILS-JGB-1741) is a potent and specific SIRT1 activity inhibitor with an IC50 of ∼15 μM. JGB1741 is a weak SIRT2 and SIRT3 inhibitor with an all IC50>100 μM. JGB1741 increases the acetylated p53 levels leading to p53-mediated apoptosis with modulation of Bax/Bcl2 ratio, cytochrome c release and PARP cleavage. JGB1741 has the potential for breast cancer research[1].

  • CAS Number: 1256375-38-8
  • MF: C27H24N2O2S
  • MW: 440.56
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 700.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 377.3±32.9 °C

Pemrametostat (GSK3326595)

GSK3326595 is a potent, selective, reversible inhibitor of protein arginine methyltransferase 5 (PRMT5) with an IC50 of 6.2 nM.

  • CAS Number: 1616392-22-3
  • MF: C24H32N6O3
  • MW: 452.549
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 760.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 413.6±32.9 °C

NSC 698600

NSC 698600 is a potent PCAF inhibitor, with IC50 of 6.51 µM (PCAF/H31-21). NSC 698600 exhibits good activity of inhibiting the proliferation of cancer cells[1].

  • CAS Number: 908069-17-0
  • MF: C14H12N2O2S
  • MW: 272.32
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC 0224

UNC0224 is a potent and selective G9a inhibitor with IC50 of 15 nM in the G9a Thioglo assay.IC50 value: 15 nM [1]Target: G9aUNC0224 (Compound 8) also potently inhibited GLP with an IC50 of 20 nM and 58 nM in the Thioglo assay and and AlphaScreen, respectively. 8 was more than 1000-fold selective for G9a over SET7/9 (a H3K4 HMT) and SET8/PreSET7 (a H4K20 HMT) in Thioglo-based biochemical assays [1] [2].

  • CAS Number: 1197196-48-7
  • MF: C26H43N7O2
  • MW: 485.665
  • Catalog: Histone Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 641.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.5±34.3 °C

DC-CPin711

DC-CPin711 is a potent and selective inhibitor of CREB-binding protein (CBP) bromodomain with an IC50 of 0.0626 μM. DC-CPin711 arrests cell cycle at G1 phase and induces apoptosis[1].

  • CAS Number: 2447559-21-7
  • MF: C23H22N4O2
  • MW: 386.45
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

666-15

666-15 is a potent and selective CREB inhibitor with an IC50 of 81 nM.

  • CAS Number: 1433286-70-4
  • MF: C33H31Cl2N3O5
  • MW: 620.522
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ep300/CREBBP-IN-3

Ep300/CREBBP-IN-3 (Example 61) is a potent Ep300 and CREBBP inhibitor with IC50s of 0.056 and 0.095 μM, respectively. Ep300/CREBBP-IN-3 can be used for the research of cancer[1].

  • CAS Number: 2259641-47-7
  • MF: C26H25F4N5O3
  • MW: 531.50
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MZP-54

MZP-54 is a selective degrader of BRD3/4 based on PROTAC technology, with a Kd of 4 nM for Brd4BD2.

  • CAS Number: 2010159-47-2
  • MF: C55H66ClN7O9S
  • MW: 1036.67
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pinometostat (EPZ5676)

Pinometostat (EPZ-5676) is a potent DOT1L histone methyltransferase inhibitor with a Ki of 80 pM.

  • CAS Number: 1380288-87-8
  • MF: C30H42N8O3
  • MW: 562.706
  • Catalog: Histone Methyltransferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 835.3±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 459.0±37.1 °C

(-)-JQ-1

(-)-JQ-1 is the stereoisomer of (+)-JQ1. (+)-JQ1 potently decreases expression of both BRD4 target genes, whereas (−)-JQ1 has no effect.

  • CAS Number: 1268524-71-5
  • MF: C23H25ClN4O2S
  • MW: 456.988
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 610.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 322.9±34.3 °C

Amodiaquine dihydrochloride

Amodiaquine dihydrochloride (Amodiaquin dihydrochloride), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor. Amodiaquine dihydrochloride is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC50 of ~20 μM. Anti-inflammatory effect[1][2][3][4].

  • CAS Number: 69-44-3
  • MF: C20H23Cl2N3O
  • MW: 392.322
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: 478ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: N/A

Bromodomain inhibitor-8

Bromodomain inhibitor-8 (Intermediate 21) is a BET bromodomain inhibitor for treating autoimmune and inflammatory diseases[1].

  • CAS Number: 1300031-70-2
  • MF: C26H25ClN2O3
  • MW: 448.94
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SNS-314

SNS-314 is a potent and selective aurora kinase inhibitor with IC50s of 9, 31, and 6 nM for aurora A, B and C, respectively[1].

  • CAS Number: 1057249-41-8
  • MF: C18H15ClN6OS2
  • MW: 430.934
  • Catalog: Aurora Kinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurora kinase inhibitor-10

Aurora kinase inhibitor-10 (Compound 6c) is an orally active Aurora B inhibitor with an IC50 of 8 nM. Aurora kinase inhibitor-10 shows antitumor activity[1].

  • CAS Number: 2417228-90-9
  • MF: C21H19F5N6O4S
  • MW: 546.47
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CRT 0066854 hydrochloride

CRT0066854 hydrochloride is a potent and selective atypical PKCs inhibitor. CRT0066854 is against full-length (FL) PKCι, PKCζ, and ROCK-II kinases with IC50 values of 132 nM, 639 nM, and 620 nM, respectively[1].

  • CAS Number: 2250019-91-9
  • MF: C24H26ClN5S
  • MW: 452.01
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MAK683 hydrochloride

MAK683 hydrochloride is an embryonic ectoderm development (EED) inhibitor extracted from patent US20160176882 A1, compound example 2. MAK683 exhibits IC50s of 59, 89, 26 nM in EED Alphascreen binding, LC-MS and ELISA assay[1][2].

  • CAS Number: 2170606-94-5
  • MF: C20H18ClFN6O
  • MW: 412.85
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TM2-115

A BIX-01294 derivative that inhibit malaria parasite histone methyltransferases, resulting in rapid and irreversible parasite death; inhibits P. falciparum 3D7 parasites in culture with IC50 of 100 nM, >22-fold more potent than IC50 toward two human cell lines and one mouse cell line; significant reduces histone H3K4me3 levels in a concentration-dependent and exposure time-dependent manner in treatment of P. falciparum parasites.

  • CAS Number: 1197196-47-6
  • MF: C29H39N5O2
  • MW: 489.664
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A