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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MK-4827(Niraparib)

Niraparib (MK-4827) is a highly potent PARP1 and PARP2 inhibitor with IC50s of 3.8 and 2.1 nM, respectively.

  • CAS Number: 1038915-60-4
  • MF: C19H20N4O
  • MW: 320.388
  • Catalog: PARP
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 463.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 234.2±28.7 °C

UNC1215

UNC1215 is a potent and selective chemical probe for the methyllysine (Kme) reading function of L3MBTL3 with Kd value of 120 nM.IC50 Value: 120 nM (Kd) [1]Target: L3MBTL3 In vitro: UNC1215 binds L3MBTL3 with a K(d) of 120 nM, competitively displacing mono- or dimethyllysine-containing peptides, and is greater than 50-fold more potent toward L3MBTL3 than other members of the MBT family while also demonstrating selectivity against more than 200 other reader domains examined. X-ray crystallography identified a unique 2:2 polyvalent mode of interaction between UNC1215 and L3MBTL3. In cells, UNC1215 is nontoxic and directly binds L3MBTL3 via the Kme-binding pocket of the MBT domains. UNC1215 increases the cellular mobility of GFP-L3MBTL3 fusion proteins, and point mutants that disrupt the Kme-binding function of GFP-L3MBTL3 phenocopy the effects of UNC1215 on localization [1].

  • CAS Number: 1415800-43-9
  • MF: C32H43N5O2
  • MW: 529.716
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 712.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.5±32.9 °C

E7016

E7016 (GPI 21016) is an orally available PARP inhibitor. E7016 can enhance tumor cell radiosensitivity in vitro and in vivo through the inhibition of DNA repair. E7016 acts as a potential anticancer agent[1][2].

  • CAS Number: 902128-92-1
  • MF: C20H19N3O3
  • MW: 349.38300
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MIR96-IN-1

MIR96-IN-1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells.Target: microRNA-96in vitro: MIR96-IN-1 inhibits biogenesis of its target precursor miRNA to varying extents : MIR96-IN-1 reduces the expression level of miR-96 by 90% at 40 μM. MIR96-IN-1 efficiently and selectively silences production of miR-96 at 40 μM while not affecting miR-182 or -183. Moreover, MIR96-IN-1 inhibits Drosha cleavage of pri-miR-96, as evidenced by an increase in the levels of pri-miR-96 and a reduction in levels of pre- and mature miR-96 in treated cells, as expected if MIR96-IN-1 binds to the Drosha site. [1]

  • CAS Number: 1311982-88-3
  • MF: C33H48N8O2
  • MW: 588.787
  • Catalog: MicroRNA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC0321

UNC0321 is a potent and selective G9a inhibitor with Ki of 63 pM, UNC0321 is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date.IC50 value: 63 pM(Ki); 9 nM (ECSD assay) [1]Target: G9aIt was found that replacing the 5-carbon chain in compound 13 with an ethoxyethyl chain resulted in compound 29{UNC0321} (IC50 = 6 nM (CLOT) and 9 nM (ECSD)), the most potent G9a inhibitor to date. 29 had a Morrison Ki of 63 pM and was about 40-fold more potent than 10 (Morrison Ki = 2.6 nM) and 250-fold more potent than 3a (Morrison Ki = 16 nM) in this G9a assay. UNC0321 potentially useful small molecule tools for the biomedical research community to investigate the biology of G9a and its role in chromatin remodeling as well as PTMs of other proteins.

  • CAS Number: 1238673-32-9
  • MF: C27H45N7O3
  • MW: 515.691
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 664.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.8±34.3 °C

TNKS-2-IN-2

TNKS-2-IN-2 is a potent and selective inhibitor of TNKS2 with an IC50 of 22 nM[1].

  • CAS Number: 2719726-91-5
  • MF: C26H23N3O6
  • MW: 473.48
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRT 1460

SRT 1460, a potent Sirtuin-1 (SIRT1) activator with an EC1.5 value of 2.9 μM, shows good selectivity for activation of SIRT1 versus SIRT2 and SIRT3 (EC1.5 > 300 μM), and is more potent than Resveratrol and the closest sirtuin homologues[1].

  • CAS Number: 925432-73-1
  • MF: C26H29N5O4S
  • MW: 507.60
  • Catalog: Sirtuin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DR 2313

DR2313 is a potent, selective, competitive and brain-penetrant inhibitor of poly(ADP-ribose) polymerase (PARP), with IC50s of 0.20 μM and 0.24 μM for PARP-1 and PARP-2, respectively. DR2313 exhibits neuroprotective effects on ischemic injuries in vitro and in vivo[1][2].

  • CAS Number: 284028-90-6
  • MF: C8H10N2OS
  • MW: 182.243
  • Catalog: PARP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 349.3±52.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 165.0±30.7 °C

EZH2-IN-15

EZH2-IN-15 (SHR2554) is a EZH2 inhibitor. EZH2-IN-15 has anti-tumor activity, and can be used for research of H3K27me3-dependent tumors[1].

  • CAS Number: 2098545-98-1
  • MF: C32H44N4O4
  • MW: 548.72
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EN884

EN884 is a BRD4 degrader via a SKP1- and proteasome-dependent manner. EN884 can be used in synthetic proteolysis targeting chimeras (PROTACs)[1].

  • CAS Number: 2189497-60-5
  • MF: C14H18N2O
  • MW: 230.31
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pyridine-3-carboxamide,hydrochloride

Nicotinamide Hydrochloride is a form of vitamin B3 or niacin that inhibits sirtuin 2 (SIRT2) activity in vitro, with an EC50 of 2 μM. Nicotinamide Hydrochloride inhibits up to 90% melanoma cell number and increases cellular NAD+, ATP, ROS levels. Nicotinamide Hydrochloride inhibts tumor growth in vivo and improves survival of melanoma-bearing mice, which can be used for the research of skin cancers such as melanoma[1].

  • CAS Number: 25334-23-0
  • MF: C6H7ClN2O
  • MW: 158.58600
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: 334.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 156ºC

DDP-38003 dihydrochloride

DDP-38003 dihydrochloride is an novel, orally available inhibitor of histone lysine-specific demethylase 1A (KDM1A/LSD1) with an IC50 of 84 nM.

  • CAS Number: 1831167-98-6
  • MF: C21H28Cl2N4O
  • MW: 423.379
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pf-03814735

PF-03814735 is a potent, orally available and reversible aurora A and aurora B inhibitor with IC50s of 0.8 and 0.5 nM, respectively.

  • CAS Number: 942487-16-3
  • MF: C23H25F3N6O2
  • MW: 474.479
  • Catalog: Aurora Kinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Heptadecyl-1,3-benzenediol

5-Heptadecylresorcinol (AR-C17), a phenolic lipid component, is also an orally active mitochondrial protector. 5-Heptadecylresorcinol improves mitochondrial function via sirtuin3 signaling pathway, thus alleviates endothelial cell damage and apoptosis. 5-Heptadecylresorcinol induces sirtuin3-mediated autophagy. 5-Heptadecylresorcinol reduces the atherosclerotic plaques in the aortic root region of mice heart. 5-Heptadecylresorcinol can be used for research of atherosclerosis prevention and obesity[1][2].

  • CAS Number: 41442-57-3
  • MF: C23H40O2
  • MW: 348.56
  • Catalog: Sirtuin
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 478.0±15.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 202.6±15.0 °C

Go 6983

Go 6983 is a pan-PKC inhibitor against for PKCα, PKCβ, PKCγ, PKCδ and PKCζ with IC50 of 7 nM, 7 nM, 6 nM, 10 nM and 60 nM, respectively.

  • CAS Number: 133053-19-7
  • MF: C26H26N4O3
  • MW: 442.510
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 709.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.6±32.9 °C

Rucaparib tartrate

Rucaparib (AG014699) tartrate is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib tartrate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib tartrate has the potential for castration-resistant prostate cancer (CRPC) research[1][2][3][4].

  • CAS Number: 773059-22-6
  • MF: C23H24FN3O7
  • MW: 473.45
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Venadaparib hydrochloride

Venadaparib (IDX-1197) hydrochloride is a potent and selective PARP inhibitor with anticancer activities. Venadaparib hydrochloride can be used for solid tumors research[1][2].

  • CAS Number: 1681020-60-9
  • MF: C23H24ClFN4O2
  • MW: 442.91
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GS-626510

GS-626510 is a potent, and orally bioavailable BET family bromodomains inhibitor, with Kd values of 0.59-3.2 nM for BRD2/3/4, with IC50 values of 83 nM and 78 nM foe BD1 and BD2, respectively[1].

  • CAS Number: 1637770-13-8
  • MF: C25H22N4O
  • MW: 394.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRT 2183

SRT 2183 is a selective Sirtuin-1 (SIRT1) activator with an EC1.5 value of 0.36 μM[1]. SRT 2183 induces growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and reduction of c-Myc protein levels[2].

  • CAS Number: 1001908-89-9
  • MF: C27H24N4O2S
  • MW: 468.57
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGP60474

CGP60474 is a potent VEGFR-2 inhibitor, with an IC50 of 84 nM, and also an ATP-competitive PKC inhibitor.

  • CAS Number: 164658-13-3
  • MF: C18H18ClN5O
  • MW: 355.82100
  • Catalog: PKC
  • Density: 1.356g/cm3
  • Boiling Point: 630.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 335.2ºC

I-BET151

I-BET151 is a BET bromodomain inhibitor which inhibits BRD4, BRD2, and BRD3 with pIC50 of 6.1, 6.3, and 6.6, respectively.

  • CAS Number: 1300031-49-5
  • MF: C23H21N5O3
  • MW: 415.444
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WP1066

WP1066 is an inhibitor of JAK2 and STAT3, and also shows effect on STAT5 and ERK1/2, without affecting JAK1 and JAK3.

  • CAS Number: 857064-38-1
  • MF: C17H14BrN3O
  • MW: 356.217
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 569.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 298.5±30.1 °C

AMPK-α1β1γ1 activator 1

AMPK-α1β1γ1 activator 1 (M1) is an acyl glucuronide metabolite of Indole-3-carboxylic Acid-based AMPK activator. AMPK-α1β1γ1 activator 1 can selectively activated human β1 isoforms with an EC50 value of 38.1nM. AMPK-α1β1γ1 activator 1 can direct binding with human AMPK α1β1γ1 isoform. AMPK-α1β1γ1 activator 1 can be used for the research of diabetic nephropathy[1].

  • CAS Number: 1943510-86-8
  • MF: C25H24ClNO9
  • MW: 517.91
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SGI-110

Guadecitabine (SGI-110) is a DNA methyltransferases (DNMT) inhibitor.

  • CAS Number: 929901-49-5
  • MF: C18H24N9O10P
  • MW: 557.411
  • Catalog: DNA Methyltransferase
  • Density: 2.2±0.1 g/cm3
  • Boiling Point: 956.4±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 532.2±37.1 °C

AK-7

AK-7 is a selective cell- and brain-permeable SIRT2 inhibitor, with an IC50 of 15.5 μM.

  • CAS Number: 420831-40-9
  • MF: C19H21BrN2O3S
  • MW: 437.351
  • Catalog: Sirtuin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nicotinamide riboside malate

Nicotinamide riboside malate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside malate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside malate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].

  • CAS Number: 2415659-01-5
  • MF: C15H20N2O10
  • MW: 388.33
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS33

MS33 is a potent WDR5 degrader, with Kds of 870 nM and 120 nM for VCB and WDR5, respectively. MS33 induces WDR5 degradation in an E3 ligase VHL, and proteasome-dependent manner. MS33 can be used for the research of acute myeloid leukemia[1][2][3].

  • CAS Number: 2407449-11-8
  • MF: C64H84F3N11O7S
  • MW: 1208.48
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Platycodin D

Platycodin D is a saponin isolated from Platycodi Radix, acts as an activator of AMPKα, with anti-obesity property[1].

  • CAS Number: 58479-68-8
  • MF: C57H92O28
  • MW: 1225.324
  • Catalog: AMPK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HPCG

2-(3-Hydroxypicolinamido)acetic acid is a 2OG oxygenase inhibitor with an IC50 value of 3.4 μM. 2-(3-Hydroxypicolinamido)acetic acid can be used as a functional probe for potential therapeutic research[1].

  • CAS Number: 3458-69-3
  • MF: C8H8N2O4
  • MW: 196.16000
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MM-589 TFA

MM-589 TFA is a potent inhibitor of WD repeat domain 5 (WDR5) and mixed lineage leukemia (MLL) protein-protein interaction. MM-589 binds to WDR5 with an IC50 of 0.90 nM and inhibits the MLL H3K4 methyltransferase activity with an IC50 of 12.7 nM[1].

  • CAS Number: 2097887-21-1
  • MF: C30H45F3N8O7
  • MW: 686.72
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A