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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Ifidancitinib

Ifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Ifidancitinib can be used in studies of allergies, asthma and autoimmune diseases[1].

  • CAS Number: 1236667-40-5
  • MF: C20H18FN5O3
  • MW: 395.39
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1003.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 560.4±34.3 °C

HDAC6/HSP90-IN-1

HDAC6/HSP90-IN-1 (compound 17) is a potent and selective dual inhibitor of HDAC6 and HSP90, with IC50 values of 4.3 and 46.8 nM, respectively. HDAC6/HSP90-IN-1 down-regulates PD-L1 expression in INF-γ treated H1975 lung cancer cells. HDAC6/HSP90-IN-1 inhibits tumor growth in human H1975 xenograft mice[1].

  • CAS Number: 2411955-43-4
  • MF: C28H37N3O6
  • MW: 511.61
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-O-Isobutyrylbritannilactone

6-O-Isobutyrylbritannilactone is a natural melanogenesis inhibitor. 6-O-Isobutyrylbritannilactone, a sesquiterpene, can be isolated from the flowers of Inula britannica. 6-O-Isobutyrylbritannilactone inhibits IBMX (HY-12318)-induced melanin production in B16F10 cells. 6-O-Isobutyrylbritannilactone also regulates ERK, PI3K/AKT, and CREB, shows antimelanogenic activity in zebrafish embryos models[1].

  • CAS Number: 1259933-02-2
  • MF: C19H28O5
  • MW: 336.42
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

INCB054329 Racemate

INCB054329 Racemate is a BET protein inhibitor.

  • CAS Number: 1628607-62-4
  • MF: C19H16N4O3
  • MW: 348.36
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET-IN-20

BET-IN-20 (compound 10) is an inhibitor of BRD4 BD1 (IC50=1.9 nM) with anticancer activity. BET-IN-20 can promote acute myeloid leukemia (AML) cell apoptosis and arrest the cell cycle in the G0/G1 phase. BET-IN-20 also inhibits c-Myc and CDK6 and enhances PARP cleavage[1].

  • CAS Number: 1300735-76-5
  • MF: C25H24N4O2
  • MW: 412.48
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2784544

Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.

  • CAS Number: 1229236-86-5
  • MF: C23H25ClFN7O
  • MW: 469.942
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-26

JAK-IN-26 (compound 2) is an orally active JAK inhibitor with good pharmacokinetic characteristics. JAK-IN-26 inhibits IFN-α2B-induced phosphorylation of STAT3 in Jurkat cells (IC50=17.2 nM)[1].

  • CAS Number: 2417134-93-9
  • MF: C22H24N6O3
  • MW: 420.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lomeguatrib

Lomeguatrib is a O6-methylguanine-DNA methyltransferase (MGMT) inhibitor, with IC50s of 9 nM in cell-free assay and ∼6 nM in MCF-7 cells.

  • CAS Number: 192441-08-0
  • MF: C10H8BrN5OS
  • MW: 326.172
  • Catalog: DNA Methyltransferase
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 683.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 367.3±34.3 °C

PF-06726304 acetate

PF-06726304 acetate is a potent and selective EZH2 inhibitor. PF-06726304 acetate inhibits wild-type and Y641N mutant EZH2 with Kis of 0.7 and 3.0 nM, respectively. PF-06726304 acetate displays robust antitumor growth activity[1].

  • CAS Number: 2080306-28-9
  • MF: C24H25Cl2N3O5
  • MW: 506.38
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YF479

YF479, a novel HDAC inhibitor, displays more potent anti-tumor activity in vitro and in vivo compared with hydroxamic acid (SAHA).

  • CAS Number: 1803281-22-2
  • MF: C22H27BrN2O5
  • MW: 479.36
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4 Inhibitor-28

BRD4 Inhibitor-28 (Compound 18) is an orally active BRD4 Inhibitor. BRD4 Inhibitor-28 inhibits BRD40-BD1, BRD40-BD2 with IC50s of 15, 55 nM. BRD4 Inhibitor-28 also inhibits BRD2-BD1, BRD3-BD1, BRDT-BD1 with IC50s of 19, 25, 68 nM. BRD4 Inhibitor-28 has anti-melanoma activity[1].

  • CAS Number: 2468960-80-5
  • MF: C23H21N3O3
  • MW: 387.43
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Methyl-2-butenoic acid [8-hydroxymethyl-1,5-dimethyl-5-(4-methyl-3-pentenyl)-12-oxabicyclo[9.1.0]dodeca-3,7-dien-2-yl] ester

Vibsanin A, a protein kinase C (PKC) activator, exhibits anti-proliferative activity against human cancer cell lines. Vibsanin A is also a HSP90 inhibitor[1].

  • CAS Number: 72506-14-0
  • MF: C25H38O4
  • MW: 402.57
  • Catalog: HSP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 501.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 158.5±23.6 °C

AMPK activator 8

AMPK activator 8 (Compound 2) is an AMP-activated protein kinase (AMPK) activator with EC50s of 11, 27, 4, 2, and 4 nM for rAMPK α1β1γ1, rAMPK α2β1γ1, rAMPK α1β2γ1, rAMPK α2β2γ1, rAMPK α2β2γ3, respectively. AMPK activator 8 can be used for the research of type 2 diabetes[1].

  • CAS Number: 1852451-96-7
  • MF: C25H21ClN2O6
  • MW: 480.90
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

iBRD4-BD1

iBRD4-BD1 is selective BRD4 bromodomain inhibitor. iBRD4-BD1 has inhibition activity for BRD4 bromodomain with an IC50 value of 12 nM. iBRD4-BD1 can be used for the research of inflammation and oncology[1].

  • CAS Number: 2839318-17-9
  • MF: C29H30F3N5O
  • MW: 521.58
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET-IN-16

BET-IN-16 (Comp I) is a BET inhibitor. BET-IN-16 shows anticancer activity. BET-IN-16 inhibits prostate cancer cell growth, with IC50 values of 0.043 and 0.034 μM against LNCaP and 22Rv1 cells, respectively[1].

  • CAS Number: 2089390-09-8
  • MF: C31H25N5O3
  • MW: 515.56
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BIX-01338 hydrate

BIX-01338 hydrate is a histone lysine methyltransferase inhibitor.

  • CAS Number: 1228184-65-3
  • MF: C32H26F3N3O7
  • MW: 621.56
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS023

MS023 is a potent, selective, and cell-active inhibitor of human type I PRMTs with IC50 of 4-119 nM.IC50 value: 4-119 nMTarget: type I PRMTs in vitro: MS023 potently inhibits PRMT1 (IC50 = 30 ± 9 nM), PRMT3 (IC50 = 119 ± 14 nM), PRMT4 (IC50 = 83 ± 10 nM), PRMT6 (IC50 = 4 ± 0.5 nM), and PRMT8 (IC50 = 5 ± 0.1 nM). Importantly, MS023 does not inhibit any type II PRMTs (PRMT5 and 9) and type III PRMT (PRMT7) at concentrations up to 10 μM. MS023 displays high potency for type I PRMTs including PRMT1, -3, -4, -6, and -8 but is completely inactive against type II and type III PRMTs, protein lysine methyltransferases and DNA methyltransferases. MS023 potently decreases cellular levels of histone arginine asymmetric dimethylation. It also reduces global levels of arginine asymmetric dimethylation and concurrently increased levels of arginine monomethylation and symmetric dimethylation in cells. [1]

  • CAS Number: 1831110-54-3
  • MF: C17H25N3O
  • MW: 287.400
  • Catalog: Histone Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 437.8±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 218.6±28.7 °C

ISOX-DUAL

ISOX-DUAL is a dual CBP/BRD4 inhibitor with IC50 values of 0.65 μM and 1.5 μM for CBP and BRD4, respectively[1].

  • CAS Number: 1962928-22-8
  • MF: C31H41N5O3
  • MW: 531.69
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 707.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.7±32.9 °C

CEM114

CEM114 is an effective chemical epigenetic modifier (CEM) that recruits endogenous chromatin machinery through CRISPR-Cas9 systems[1].

  • CAS Number: 2279062-54-1
  • MF: C84H122FN9O19S
  • MW: 1612.98
  • Catalog: CRISPR/Cas9
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRK-740

MRK-740 is a potent, selective and substrate-competitive PRDM9 histone methyltransferase inhibitor with an IC50 of 80 nM. MRK-740 is more selective for PRDM9 than other histone methyltransferases and other non-epigenetic targets. MRK-740 reduces PRDM9-dependent trimethylation of H3K4 (IC50 = 0.8 µM)[1].

  • CAS Number: 2387510-80-5
  • MF: C25H32N6O3
  • MW: 464.56
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mefuparib hydrochloride(CVL218)

Mefuparib hydrochloride is a potent, highly selective, competitive PARP1/2 inhibitor with IC50 of 3.2/1.9 nM, respectively; displays >406-fold over other major nuclear PARPs including PARP3, TNKS1, TNKS2 and PARP6; reduces poly(ADP-ribose) formation, enhances γH2AX levels, induces G2/M arrest and subsequent apoptosis in homologous recombination repair (HR)-deficient cells; shows potent in vitro and in vivo proliferation and growth inhibition against HR-deficient cancer cells and synergistic sensitization of HR-proficient xenografts to the anticancer drug temozolomide.

  • CAS Number: 1449746-00-2
  • MF: C17H16ClFN2O2
  • MW: 334.775
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IMM-H007

IMM-H007 is a potent TGFβ1 (transforming growth factor β1) antagonist. IMM-H007 has protective effects in cardiovascular diseases via activation of AMPK (AMP-activated protein kinase). IMM-H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. IMM-H007 inhibits ABCA1 degradation. IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. IMM-H007 can be used for the research of nonalcoholic fatty liver disease (NAFLD) and inflammatory atherosclerosis[1][2][3].

  • CAS Number: 1221412-23-2
  • MF: C22H23N5O8
  • MW: 485.45
  • Catalog: AMPK
  • Density: 1.54±0.1 g/cm3
  • Boiling Point: 684.6±65.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-64619178

JNJ-64619178 is a selective and pseudo-irreversible PRMT5 inhibitor[1].

  • CAS Number: 2086772-26-9
  • MF: C22H23BrN6O2
  • MW: 483.36
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC4-IN-1

HDAC4-IN-1 (compound 1a) is a class IIa HDACI inhibitor (IC50=0.077 μM). HDAC4-IN-1 can enhance Caspase-induced Apoptosis. HDAC4-IN-1 has anticancer activity. HDAC4-IN-1 can be used in the research of drug combination against cancer[1].

  • CAS Number: 1418293-39-6
  • MF: C16H19F3N4O2
  • MW: 356.34
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LLY 507

LLY-507 is a potent and selective inhibitor of protein-lysine methyltransferase SMYD2 with an IC50 of 15 nM.

  • CAS Number: 1793053-37-8
  • MF: C36H42N6O
  • MW: 574.758
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 790.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 431.8±35.7 °C

CMP-5

CMP-5 (PRMT5-IN-5)is a first-in-class, small-molecule PRMT5-specific inhibitor that blocks EBV-driven B-lymphocyte transformation and survival, without effect on normal B cells; displays no activity against other type I (PRMT1 and PRMT4) and type II (PRMT7) enzymes; inhibition of PRMT5 leads to lost recruitment of a PRMT5/p65/HDAC3-repressive complex on the miR96 promoter, restored miR96 expression, and PRMT5 downregulation.

  • CAS Number: 880813-42-3
  • MF: C21H21N3
  • MW: 315.411
  • Catalog: Histone Methyltransferase
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 505.1±48.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 259.3±29.6 °C

PF CBP1

PF-CBP1 is a highly selective inhibitor of the CREB binding protein bromodomain[1].

  • CAS Number: 1962928-21-7
  • MF: C29H36N4O3
  • MW: 488.621
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 673.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 361.1±31.5 °C

GSK2879552 dihydrochloride

GSK2879552 dihydrochloride an orally active, selective and irreversible inhibitor of lysine specific demethylase 1 (LSD1/KDM1A), with potential antineoplastic activity[1][2].

  • CAS Number: 1902123-72-1
  • MF: C23H30Cl2N2O2
  • MW: 437.40
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EZH2-IN-4

EZH2-IN-4 is an orally active, potent EZH2 inhibitor with IC50s of 0.923 nM and 2.65 nM against wild type (WT) 5-membered (5-mer) EZH2 and mutant 5-mer EZH2, respectively. EZH2-IN-4 has anti-cancer activity[1].

  • CAS Number: 2088132-99-2
  • MF:
  • MW:
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY 598

BAY-598 is selective small molecule inhibitor of SMYD2 .

  • CAS Number: 1906919-67-2
  • MF: C22H20Cl2F2N6O3
  • MW: 525.34
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A