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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PBRM1-BD2-IN-1

PBRM1-BD2-IN-1 is a selective and cell-active polybromo-1 (PBRM1) bromodomain inhibitor. PBRM1-BD2-IN-1 has binding affinity and inhibitory activity for PBRM1-BD2 with Kd and IC50 values of 0.7 μM and 0.2 μM, respectively. PBRM1-BD2-IN-1 can be used for the research of cancer[1].

  • CAS Number: 1915012-21-3
  • MF: C17H19ClN2O
  • MW: 302.80
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vorinostat(SAHA)

Vorinostat is a potent and orally available inhibitor of HDAC1, HDAC2 and HDAC3 (Class I), HDAC7 (Class II) and HDAC11 (Class IV ), with ID50 values of 10 nM and 20 nM for HDAC1 and HDAC3, respectively.

  • CAS Number: 149647-78-9
  • MF: C14H20N2O3
  • MW: 264.320
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 161-162°C
  • Flash Point: N/A

Malvidin-3-O-arabinoside chloride

Malvidin-3-O-arabinoside chloride ameliorates ethyl carbamate-induced oxidative damage by stimulating AMPK-mediated autophagy[1].

  • CAS Number: 28500-04-1
  • MF: C22H23O11.Cl
  • MW: 498.864
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD9 Degrader-1

PROTAC BRD9 Degrader-1 is a lead PROTAC BRD9 chemical degrader, which can be used as a selective probe useful for the study of BAF complex biology[1].

  • CAS Number: 2097971-01-0
  • MF: C42H45N7O12S2
  • MW: 903.98
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MI-2

MI-2 is a Menin-MLL interaction inhibitor with IC50 of 446±28 nM.

  • CAS Number: 1271738-62-5
  • MF: C18H25N5S2
  • MW: 375.555
  • Catalog: Histone Methyltransferase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 538.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 279.2±32.9 °C

Z26395438

Z26395438 (compound 1) is a potent Sirtuin-1 inhibitor, with an IC50 value of 1.6 μM[1].

  • CAS Number: 2803-63-6
  • MF: C17H15FN2O
  • MW: 282.31
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4 Inhibitor-15

BRD4 Inhibitor-15 (compound 13) is a potent BRD4 inhibitor, with an IC50 of 18 nM. BRD4 Inhibitor-15 induces apoptosis of 22RV1 cells by regulating Bcl-2/Bax proteins and activating caspase-3 signaling pathway. BRD4 Inhibitor-15 down-regulates the c-Myc level in 22RV1 cells. BRD4 Inhibitor-15 can be used for prostate cancer research[1].

  • CAS Number: 2761366-60-1
  • MF: C22H21N3O2
  • MW: 359.42
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRCA1-IN-1

BRCA1-IN-1 is a novel small-molecule-like BRCA1 inhibitor with IC50 and Ki of 0.53 μM and 0.71 μM, respecrively.

  • CAS Number: 1622262-74-1
  • MF: C27H33F2N4O6P
  • MW: 578.54
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DCP-LA

DCP-LA (FR236924), a linoleic acid derivative, selectively and directly activates PKCε[1].

  • CAS Number: 28399-31-7
  • MF: C20H36O2
  • MW: 308.50
  • Catalog: PKC
  • Density: 0.969g/cm3
  • Boiling Point: 417.047ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 184.49ºC

JQEZ5

JQEZ5 is a novel and potent EZH2 inhibitor.

  • CAS Number: 1913252-04-6
  • MF: C30H38N8O2
  • MW: 542.68
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-MRTX-1719

(S)-MRTX-1719 (example 16-7) is the S-enantiomer of MRTX-1719. (S)-MRTX-1719 is a PRMT5/MTA complex inhibitor, with an IC50 of 7070 nM[1].

  • CAS Number: 2630904-44-6
  • MF: C23H18ClFN6O2
  • MW: 464.88
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Entinostat (MS-275)

Entinostat is an oral and selective class I HDAC inhibitor, with IC50s of 243 nM, 453 nM, and 248 nM for HDAC1, HDAC2, and HDAC3, respectively.

  • CAS Number: 209783-80-2
  • MF: C21H20N4O3
  • MW: 376.409
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 566.7±50.0 °C at 760 mmHg
  • Melting Point: 159-160ºC
  • Flash Point: 296.6±30.1 °C

WZ 4003

WZ4003 is the first potent and highly specific NUAK kinase inhibitor with IC50 of 20 nM/100 nM for NUAK1/NUAK2, without significant inhibition on other 139 kinases.

  • CAS Number: 1214265-58-3
  • MF: C25H29ClN6O3
  • MW: 496.989
  • Catalog: AMPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phenformin (hydrochloride)

Phenformin (hydrochloride) is a hydrochloride salt of phenformin that is an anti-diabetic drug from the biguanide class, can activate AMPK activity.

  • CAS Number: 834-28-6
  • MF: C10H16ClN5
  • MW: 241.721
  • Catalog: AMPK
  • Density: 1.24 g/cm3
  • Boiling Point: 413.7ºC at 760 mmHg
  • Melting Point: 175-178ºC
  • Flash Point: 204ºC

PJ34 HCl

PJ34 hydrochloride is an inhibitor of PARPl1/2 with IC50 of 110 nM and 86 nM, respectively.

  • CAS Number: 344458-15-7
  • MF: C17H18ClN3O2
  • MW: 331.80
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: 539.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 279.9ºC

Pumecitinib

Pumecitinib is a Janus kinase (JAK) inhibitor with anti-inflammatory activity[1].

  • CAS Number: 2401057-12-1
  • MF: C17H20N8O2S
  • MW: 400.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-41

HDAC-IN-41 (Compound 7c) is a selective, orally active class I HDAC inhibitor with IC50 values of 0.62, 1.46 and 0.62 μM against HDAC1, HDAC2 and HDAC3, respectively. HDAC-IN-41 shows NO releasing activity[1].

  • CAS Number: 2490309-83-4
  • MF: C20H22N4O6S
  • MW: 446.48
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRTX-1719

MRTX-1719 is a potent first-in-class selective inhibitor of the PRMT5/MTA complex, with an IC50 of less than 10 nM in PRMT5/MTA MTAPDEL SDMA cells[1].

  • CAS Number: 2630904-45-7
  • MF: C23H18ClFN6O2
  • MW: 464.88
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DS-9300

DS-9300 is a potent, orally active, selective EP300/CBP HAT inhibitor with an IC50 value of 28 nM. DS-9300 has anticancer activity and can be used in prostate cancer disease research[1].

  • CAS Number: 2259641-46-6
  • MF: C25H26F3N5O3
  • MW: 501.50
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pulrodemstat

Pulrodemstat (CC-90011) is a potent, selective, reversible and orally active inhibitor of lysine specific demethylase-1 (LSD1) with an IC50 of 0.25 nM. Pulrodemstat is less enzymatic inhibition against LSD2, MOA-A, and MAO-B. Pulrodemstat induces acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cells differentiation and has potent anticancer activity[1].

  • CAS Number: 1821307-10-1
  • MF: C24H23F2N5O2
  • MW: 451.47
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC3 Inhibitor (Histone Deacetylase 3)

HDAC3-IN-1 (compound 5) is a potent and selective HDAC3 inhibitor, with an IC50 of 5.96 nM[1].

  • CAS Number: 2044701-99-5
  • MF: C20H23N3O2
  • MW: 337.42
  • Catalog: HDAC
  • Density: 1.140±0.06 g/cm3(Predicted)
  • Boiling Point: 562.5±50.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

MZP-55

MZP-55 is a selective degrader of BRD3/4 based on PROTAC technology, with a Kd of 8 nM for Brd4BD2.

  • CAS Number: 2010159-48-3
  • MF: C57H70ClN7O10S
  • MW: 1080.72
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC1/2 and CDK2-IN-1

HDAC1/2 and CDK2-IN-1 (compound 14d) is a potent HDAC1, HDAC2 and CDK2 dual inhibitor, with IC50 values of 70.7, 23.1 and 0.80 μM, respectively. HDAC1/2 and CDK2-IN-1 can block the cell cycle and induce apoptosis. HDAC1/2 and CDK2-IN-1 exhibits desirable in vivo antitumor activity[1].

  • CAS Number: 2418559-01-8
  • MF: C26H22ClN7O
  • MW: 483.95
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC 2400

UNC2400 is a close analog of UNC1999 with >1,000-fold lower potency than UNC1999 as a negative control for cell-based studies[1][2].

  • CAS Number: 1433200-49-7
  • MF: C35H47N7O2
  • MW: 597.793
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 798.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 436.6±32.9 °C

PROTAC BRD9-binding moiety 1

Target Protein-binding moiety 6 is a compound that binds to BRD9, and used for inhibiting BRD9 activity.

  • CAS Number: 2097512-23-5
  • MF: C23H25N3O7S2
  • MW: 519.59
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nanafrocin

Nanaomycin A is the first selective DNMT3B inhibitor with an IC50 of 500 nM. Nanaomycin A, a quinone antibiotics, reactivates silenced tumor suppressor genes in human cancer cells[1]. Nanaomycin A inhibits in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM[2].

  • CAS Number: 52934-83-5
  • MF: C16H14O6
  • MW: 302.279
  • Catalog: DNA Methyltransferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 601.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 229.0±25.0 °C

EBI-2511

EBI-2511 is a highly potent and orally active EZH2 inhibitor, with an IC50 of 6 nM in Pfeffiera cell lines, respectively.

  • CAS Number: 2098546-05-3
  • MF: C34H48N4O4
  • MW: 576.77
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tanshinol borneol ester

Tanshinol borneol ester, an angiogenesis stimulator, promoted multiple key steps of angiogenesis through Akt and MAPK signalling pathways. Tanshinol borneol ester has anti-ischemic and anti-atherosclerosis activities[1].

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

Fedratinib(SAR302503,TG101348)

Fedratinib (TG-101348) is a selective inhibitor of JAK2 with an IC50 of 3 nM, showing 35- and 334-fold selectivity over JAK1 and JAK3, respectively.

  • CAS Number: 936091-26-8
  • MF: C27H36N6O3S
  • MW: 524.678
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 713.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 385.5±35.7 °C

C7280948

C-7280948 is a PRMT1 inhibitor.IC50 value:Target: PRMT1in vitro: Especially arginine methyltransferases also target non-histone protein substrates and are therefore often called protein methyltransferases (PRMTs). The subtype PRMT1 has been linked to the activation of estrogen and androgen receptors and therefore may represent a new treatment option for hormone-dependent cancer. C-7280948 is a inhibitor, which is available for PRMT1.

  • CAS Number: 587850-67-7
  • MF: C14H16N2O2S
  • MW: 276.354
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 481.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.8±31.5 °C