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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Trimethylapigenin

5,7,4'-Trimethoxyflavone is isolated from Kaempferia parviflora (KP) that is a famous medicinal plant from Thailand. 5,7,4'-Trimethoxyflavone induces apoptosis, as evidenced by increments of sub-G1 phase, DNA fragmentation, annexin-V/PI staining, the Bax/Bcl-xL ratio, proteolytic activation of caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein.5,7,4'-Trimethoxyflavone is significantly effective at inhibiting proliferation of SNU-16 human gastric cancer cells in a concentration dependent manner[1].

  • CAS Number: 5631-70-9
  • MF: C18H16O5
  • MW: 312.31700
  • Catalog: Apoptosis
  • Density: 1.242g/cm3
  • Boiling Point: 506.5ºC at 760mmHg
  • Melting Point: 158-160ºC (dec.)
  • Flash Point: 225.5ºC

Rucaparib (AG-014699) phosphate

Rucaparib (AG-014699, PF-01367338) is a potent and oral PARP1/2/3 inhibitor, with a Ki of 1.4 nM for PARP1 in cell-free assay, also showing binding affinity to eight other PARP domains.

  • CAS Number: 459868-92-9
  • MF: C19H21FN3O5P
  • MW: 421.359
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: 625.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 331.9ºC

PAD2-IN-2

PAD2-IN-2 is a potent PAD2 inhibitor. PAD2-IN-2 enters the HEK293T/PAD2 cells with an EC50 of 5.9 μM. PAD2-IN-2 inhibits histone H3 citrullination with an EC50 of 2.1 μM in HEK293/PAD2 cells. PAD2-IN-2 can be used for the research of cancer[1].

  • CAS Number: 2095107-57-4
  • MF: C24H27FN6O3
  • MW: 466.508
  • Catalog: Cancer
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP-IN-1

CBP-IN-1 is a potent p300/CBP bromodomain inhibitor[1].

  • CAS Number: 2222941-37-7
  • MF: C30H32F2N4O3
  • MW: 534.60
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-30

JAK-IN-30 (compound 31) is a water-soluble JAK inhibitor with IC50 values of 2, 15, 18 and 2 nM for JAK2, JAK1, JAK3 and TYK2, respectively. JAK-IN-30 has research potential for dry eye disease (DED)[1].

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

CypD-IN-3

CypD-IN-3 is a potent and subtype-selective cyclophilin D (CypD) inhibitor. CypD-IN-3 has CypD affinity with an IC50 value of 0.01 μM. CypD-IN-3 can be used for the research of several diseases including oxidative stress, neurodegenerative disorders, liver diseases, aging, autophagy and diabetes[1].

  • CAS Number: 2651994-75-9
  • MF: C53H61N7O11
  • MW: 972.09
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Peficitinib hydrochloride

Peficitinib (ASP015K) hydrochloride is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively[1].

  • CAS Number: 1353219-06-3
  • MF: C18H23ClN4O2
  • MW: 362.85
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP-2/1-IN-2

PARP-2/1-IN-2 (Compound 4a), the enantiomer of Veliparib (HY-10129), is a potent PARP inhibitor with Kis of 2 and 5 nM against PARP-2 and PARP-1, respectively. PARP-2/1-IN-2 has an EC50 of 3 nM in a cell based assay of PARP activity[1].

  • CAS Number: 912444-01-0
  • MF: C13H24N4O
  • MW: 252.356
  • Catalog: PARP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 466.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 235.9±28.7 °C

Cambinol

Cambinol is a SIRT1 and SIRT2 inhibitor with IC50 values of 56 and 59 μM, respectively.

  • CAS Number: 14513-15-6
  • MF: C21H16N2O2S
  • MW: 360.429
  • Catalog: Sirtuin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 667ºC at 760mmHg
  • Melting Point: 235 °C(dec.)
  • Flash Point: 357.2ºC

CDK8-IN-12

CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent[1].

  • CAS Number: 2613307-67-6
  • MF: C21H20ClN3O2
  • MW: 381.86
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Apicidin

Apicidin (OSI 2040) is a fungal metabolite, acts as a histone deacetylase (HDAC) inhibitor, with antiparasitic activity and a broad spectrum antiproliferative activity[1].

  • CAS Number: 183506-66-3
  • MF: C34H49N5O6
  • MW: 609.75600
  • Catalog: HDAC
  • Density: 1.27g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-GSK-3685032

(R)-GSK-3685032 is the R-enantiomer of GSK-3685032. GSK-3685032 is a non-time-dependent, noncovalently, first-in-class reversible DNMT1-selective inhibitor, with an IC50 of 0.036 μM. GSK-3685032 induces robust loss of DNA methylation, transcriptional activation, and cancer cell growth inhibition[1][2].

  • CAS Number: 2170140-50-6
  • MF: C22H24N6OS
  • MW: 420.53
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EPZ005687

EPZ005687 is a potent and selective inhibitor of EZH2 with Ki of 24 nM, and has 50-fold selectivity against EZH1 and 500-fold selectivity against 15 other protein methyltransferases.

  • CAS Number: 1396772-26-1
  • MF: C32H37N5O3
  • MW: 539.668
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 797.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 436.4±32.9 °C

Guttiferone G

Guttiferone G inhibits recombinant human SIRT1 and SIRT2 (IC50: 9 and 22 μM, respectively). Guttiferone G is weakly cytotoxic in A2780 human ovarian cell line (IC50: 8.0 μg/mL). Guttiferone G can be isolated from Garcinia macrophylla[1][2].

  • CAS Number: 666174-75-0
  • MF: C43H58O6
  • MW: 670.92
  • Catalog: Sirtuin
  • Density: 1.088±0.06 g/cm3(Predicted)
  • Boiling Point: 756.4±60.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Karanjin

Karanjin is a major active furanoflavonol constituent of Fordia cauliflora. Karanjin induces GLUT4 translocation in skeletal muscle cells by increasing AMPK activity. Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis[1][2].

  • CAS Number: 521-88-0
  • MF: C18H12O4
  • MW: 292.285
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 463.0±45.0 °C at 760 mmHg
  • Melting Point: 156ºC
  • Flash Point: 233.8±28.7 °C

GSK-3685032

GSK-3685032 is a non-time-dependent, noncovalently, first-in-class reversible DNMT1-selective inhibitor, whit an IC50 of 0.036 μM. GSK-3685032 induces robust loss of DNA methylation, transcriptional activation and cancer cell growth inhibition[1].

  • CAS Number: 2170137-61-6
  • MF: C22H24N6OS
  • MW: 420.53
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A 366

A-366 is a potent histone methyltransferase G9a inhibitor with an IC50 of 3.3 nM.

  • CAS Number: 1527503-11-2
  • MF: C19H27N3O2
  • MW: 329.43700
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BCI-121

BCI-121 is a SMYD3 inhibitor that impairs the proliferation of cancer cell.

  • CAS Number: 432529-82-3
  • MF: C14H18BrN3O2
  • MW: 340.216
  • Catalog: Histone Methyltransferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 576.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 302.2±30.1 °C

D-Cl-amidine

D-Cl-amidine is a potent and highly selective PAD1 inhibitor. D-Cl-amidine is well-torelated with no significant toxicity[1].

  • CAS Number: 1404060-15-6
  • MF: C14H19ClN4O2
  • MW: 310.78
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desmethyltamoxifen hydrochloride

N-Desmethyltamoxifen hydrochloride is the major metabolite of tamoxifen in humans. N-Desmethyltamoxifen, a poor antiestrogen, is a ten-fold more potent protein kinase C (PKC) inhibitor than Tamoxifen. N-Desmethyltamoxifen hydrochloride is also a potent regulator of ceramide metabolism in human AML cells, limiting ceramide glycosylation, hydrolysis, and sphingosine phosphorylation[1][2][3].

  • CAS Number: 15917-65-4
  • MF: C25H28ClNO
  • MW: 393.94900
  • Catalog: PKC
  • Density: 1.047g/cm3
  • Boiling Point: 485.8ºC at 760mmHg
  • Melting Point: 225-227ºC
  • Flash Point: 213.2ºC

DW14800

DW14800 is a protein arginine methyltransferase 5 (PRMT5) inhibitor, with an IC50 of 17 nM. DW14800 reduces H4R3me2s levels and enhances the transcription of HNF4α, but does not alter PRMT5 expression. Anti-cancer activity[1].

  • CAS Number: 2243709-60-4
  • MF: C31H36N4O3
  • MW: 512.64
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-207

GNE-207 is a potent, selective and orally bioavailable inhibitor of the bromodomain of CBP, with an IC50 of 1 nM, a selectively index of >2500-fold against BRD4 (1) (IC50, 3.1 μM)[1]. GNE-207 shows excellent CBP potency, with an EC50 of 18 nM for MYC expression in MV-4-11 cells[1].

  • CAS Number: 2158266-58-9
  • MF: C29H30N6O3
  • MW: 510.59
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydrocoumarin

Dihydrocoumarin is a compound found in Melilotus officinalis. Dihydrocoumarin is a yeast Sir2p inhibitor. Dihydrocoumarin also inhibits human SIRT1 and SIRT2 with IC50s of 208 μM and 295 μM, respectively[1].

  • CAS Number: 119-84-6
  • MF: C9H8O2
  • MW: 148.159
  • Catalog: Sirtuin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 272.0±15.0 °C at 760 mmHg
  • Melting Point: 24-25 °C(lit.)
  • Flash Point: 108.4±17.8 °C

5-Carboxy-8-hydroxyquinoline

IOX1 is the most potent broad-spectrum inhibitor of 2OG oxygenases, including the JmjC demethylases; IC50 for KDM4A/KDM3A is 0.6/0.1 uM.IC50 value: 0.6/0.1 uM(KDM4A/KDM3A) [1]Target: JmjC KDMs inhibitorIOX1 is the most potent against a representative panel of 2OG oxygenases, including non-JmjC 2OG oxygenases, with an in vitro IC50 value in the micromolar range. However, its efficacy in cells is about a hundred-fold lower (HeLa cells, KDM4A, IC50 = 86uM), possibly due to low cell permeability resulting from itspolar C-5 carboxyl group.

  • CAS Number: 5852-78-8
  • MF: C10H7NO3
  • MW: 189.167
  • Catalog: Histone Demethylase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 464.5±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 234.7±24.6 °C

p32 inhibitor M36

p32 inhibitor M36 (M36) is a p32 mitochondrial protein inhibitor, which binds directly to p32 and inhibits p32 association with LyP-1[1].

  • CAS Number: 802555-85-7
  • MF: C23H28N8O2
  • MW: 448.52
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Peficitinib hydrobromide

Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

  • CAS Number: 1353219-05-2
  • MF: C18H23BrN4O2
  • MW: 407.30
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC0379 trifluoroacetate salt

UNC0379 trifluoroacetate is a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8 with IC50 of 7.3±1.0 uM; selective over 15 other methyltransferases.IC50 value: 7.3±1.0 uMTarget: SETD8 inhibitorUNC0379 is a synthetic small-molecule inhibitor that displays inhibitory activity in multiple biochemical assays and is selective for SETD8 over 15 other methyltransferases. The binding affinity of UNC0379 to SETD8 was determined using biophysical assays such as ITC (isothermal titration calorimetry) and SPR (surface plasmon resonance) and is largely consistent with its potency in biochemical assays.

  • CAS Number: 1620401-83-3
  • MF: C25H36F3N5O4
  • MW: 527.580
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bisindolylmaleimide VIII acetate

Bisindolylmaleimide VIII acetate (Ro 31-7549 acetate) is a potent and selective protein kinase C (PKC) inhibitor with an IC50 of 158 nM for rat brain PKC. Bisindolylmaleimide VIII acetate has IC50s of 53, 195, 163, 213, and 175 nM for PKC-α, PKC-βI, PKC-βII, PKC-γ, PKC-ε, respectively[1]. Bisindolylmaleimide VIII acetate facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases[2].

  • CAS Number: 138516-31-1
  • MF: C26H26N4O4
  • MW: 458.509
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 693ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 372.9ºC

KDM-IN-6

KDM2A/7A-IN-1 is a first-in-class, selective and cell-permeable inhibitor of histone lysine demethylases KDM2A/7A, with an IC50 of 0.16 μM for KDM2A, exhibits 75 fold selevtivity over other JmjC lysine demethylases, and is inactive on methyl transferases, and histone acetyl transferases[1].

  • CAS Number: 2169272-46-0
  • MF: C33H38N4O
  • MW: 506.68
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI-9564

BI-9564 is a selective, and cell-permeable BRD9 BD inhibitor, with Kd of 5.9 nM for BRD9, and IC50 of > 100 μM for BET family.

  • CAS Number: 1883429-22-8
  • MF: C20H23N3O3
  • MW: 353.415
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 519.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 268.3±30.1 °C