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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N-(4-(4-(3-Methyl-1H-pyrazol-5-ylamino)-6-(4-Methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)propionamide

VE-465 is an Aurora kinase inhibitor. VE-465 induces cancer cell apoptosis. VE-465 has anticancer effects in multiple tumor models[1][2].

  • CAS Number: 639089-73-9
  • MF: C22H28N8OS
  • MW: 452.576
  • Catalog: Aurora Kinase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MRT 199665

MRT 199665 is a potent salt-inducible kinases (SIKs) inhibitor with IC50 of 110, 12, 43 nM for SIK1,2,3 respectively; also inhibits AMPKα1/α2 (both IC50=10 nM), MARK1/2/3/4 (both IC50=2 nM), NUAK1/2 (IC50=3/120 nM), and MELK (IC50=29 nM); elevates IL-10 production by inducing the dephosphorylation of CREB-regulated transcriptional coactivator 3 (CRTC3), increases LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion (IL-6, IL-12, and TNF) in macrophages.

  • CAS Number: 1456858-57-3
  • MF: C18H19N3O4S
  • MW: 373.43
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BPTF-IN-1

BPTF-IN-1 (compound AU1) is a selective bromodomain and PHD finger containing transcription factor (BPTF) bromodomain inhibitor with a Kd of 2.8 μM. BPTF-IN-1 shows to be selective for BPTF over BRD4 bromodomain. BPTF-IN-1 shows antimalarial activity[1].

  • CAS Number: 2359618-49-6
  • MF: C23H23FN6O3
  • MW: 450.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WDR5-IN-1

WDR5-IN-1 is a potent and selective WD repeat domain 5 (WDR5) inhibitor, with a Kd of <0.02 nM. WDR5-IN-1 inhibits MLL1 histone methyltransferase (HMT) activity with an IC50 of 2.2 nM. WDR5-IN-1 diminishes MYC recruitment at WDR5-displaced genes and exhibits potent anti-proliferative effects in CHP-134 (neuroblastoma) and Ramos (Burkitt’s lymphoma) lines[1].

  • CAS Number: 2408842-51-1
  • MF: C30H31FN4O3
  • MW: 514.59
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ-3

AZ-3 is a potent and selective JAK1 inhibitor with an IC50 of 34 nM.

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

Gnetol

Gnetol is a phenolic compound isolated from the root of Gnetum ula Brongn. Gnetol potently inhibits COX-1 (IC50 of 0.78 μM) and HDAC. Gnetol is a potent tyrosinase inhibitor with an IC50 of 4.5 μM for murine tyrosinase and suppresses melanin biosynthesis. Gnetol has antioxidant, antiproliferative, anticancer and hepatoprotective activity. Gnetol also possesses concentration-dependent α-Amylase, α-glucosidase, and adipogenesis activities[1][2][3].

  • CAS Number: 86361-55-9
  • MF: C14H12O4
  • MW: 244.243
  • Catalog: HDAC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 540.8±30.0 °C at 760 mmHg
  • Melting Point: 87 - 90ºC
  • Flash Point: 269.7±19.2 °C

SIRT6-IN-1

SIRT2/6-IN-1 (Compound 5) is a SIRT6/SIRT2 inhibitor, with IC50s of 106 μM and 114 μM. SIRT2/6-IN-1 increases H3K9 acetylation, increases glucose uptake and reduces TNF-α secretion in cells[1].

  • CAS Number: 1214468-35-5
  • MF: C19H14N4O5S
  • MW: 410.40
  • Catalog: Sirtuin
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06700841 P-Tosylate

PF-06700841 P-Tosylate is a dual JAK1 and TYK2 inhibitor with IC50s of 17 and 23 nM, respectively. Anti-inflammatory activity[1].

  • CAS Number: 2140301-96-6
  • MF: C25H29F2N7O4S
  • MW: 561.60
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-14

PRMT5-IN-14 is a PRMT5 inhibitor to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

  • CAS Number: 2278356-90-2
  • MF: C18H18Cl2N4O4
  • MW: 425.27
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vaccarin

Vaccarin is an active flavonoid glycoside associated with various biological functions. Vaccarin significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK signaling pathway[1][2].

  • CAS Number: 53452-16-7
  • MF: C32H38O19
  • MW: 726.633
  • Catalog: AMPK
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 1088.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 345.6±27.8 °C

HTH 01-015

HTH-01-015 is a selective NUAK1 inhibitor (IC50 is 100 nM). HTH-01-015 inhibits NUAK1 with >100-fold higher potency than NUAK2 (IC50 of >10 μM).

  • CAS Number: 1613724-42-7
  • MF: C26H28N8O
  • MW: 468.553
  • Catalog: AMPK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 759.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 413.2±35.7 °C

LSD1-IN-13 hydrochloride

LSD1-IN-13 hydrochloride (compound 7e) is an orally active and potent LSD1 inhibitor, with an IC50 of 24.43 nM. LSD1-IN-13 hydrochloride can activate CD86 expression, with an EC50 of 470 nM. LSD1-IN-13 hydrochloride induces differentiation of AML (acute myeloid leukemia) cell lines[1].

  • CAS Number: 2170347-90-5
  • MF: C23H30ClN3O2S
  • MW: 448.02
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD1152

AZD1152 is a pro-drug of Barasertib-hQPA, which is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay.

  • CAS Number: 722543-31-9
  • MF: C26H31FN7O6P
  • MW: 587.540
  • Catalog: Aurora Kinase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC0379

UNC0379 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: 1620401-82-2
  • MF: C23H35N5O2
  • MW: 413.556
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 606.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 320.5±34.3 °C

CM-272

CM-272 (CM272) is a novel potent, selective and reversible dual inhibitor of G9a/DNMTs with IC50 of 8 nM and 382 nM for G9a and DNMT1, respectively; also inhibits DNMT3A/3B/GLP with IC50 of 85/1,200/2 nM, respectively; inhibits cell proliferation and promotes apoptosis in different haematological neoplasias (AML, ALL and DLBCL); significantly prolongs survival of AML, ALL and DLBCL xenogeneic models.

  • CAS Number: 1846570-31-7
  • MF: C28H38N4O3
  • MW: 478.626
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 631.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 336.0±31.5 °C

MI-463

MI-463 is a highly potent and orally bioavailable small molecule inhibitor of the menin-mLL interaction.

  • CAS Number: 1628317-18-9
  • MF: C24H23F3N6S
  • MW: 484.540
  • Catalog: Histone Methyltransferase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 663.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.9±31.5 °C

BI-7273

BI-7273 is a selective, and cell-permeable BRD9 inhibitor, with an IC50 and a Kd of 19 and 0.75 nM; also shows high effect on BRD7, with an IC50 and a Kd of 117 nM and 0.3 nM.

  • CAS Number: 1883429-21-7
  • MF: C20H23N3O3
  • MW: 353.415
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 509.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 261.8±30.1 °C

Itf3756

ITF3756 is a selective histone deacetylase 6 (HDAC6) inhibitor bearing a pentaheterocyclic scaffold.

  • CAS Number: 2247608-27-9
  • MF: C13H11N5O2S
  • MW: 301.32
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BML-266

JFD00244 is a sirtuin 2 (SIRT2) inhibitor. Anti-tumor effect[1].

  • CAS Number: 96969-83-4
  • MF: C30H26N2O4
  • MW: 478.538
  • Catalog: Sirtuin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 780.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 425.7±32.9 °C

PNZ5

PNZ5 is a potent and isoxazole-based pan-BET inhibitor with high selectivity and potency similar to the well-established (+)-JQ1, with a KD of 5.43 nM for BRD4(1)[1].

  • CAS Number: 1629277-36-6
  • MF: C20H18N2O2
  • MW: 318.37
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MR837

MR837 is an inhibitor of NSD2-PWWP1. MR837 can bind with human nuclear receptor binding SET domain protein 2 (PWWP domain)[1].

  • CAS Number: 1210906-48-1
  • MF: C16H14N2OS
  • MW: 282.36
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06679142

PF-06679142 is a novel potent, orally active, α1β1γ1/α2β1γ1-isoform selective AMPK activator with Kd of 14 nM, EC50 of 22 nM for α1β1γ1-AMPK, shows minimal activity at the β2-containing isoforms (α1β2γ1, α2β2γ1, α2β2γ3); demonstrates in vivo target engagement experiment in ZSF-1 rats, an obese/diabetic rodent model of diabetic nephropathy.

  • CAS Number: 1467059-66-0
  • MF: C20H17F2NO3
  • MW: 357.357
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Balanol

Balanol (Ophiocordin; Azepinostatin) is a potent and ATP competitive PKC/PKA inhibitor against human PKC isozymes α, β-I, β-II, γ, δ, ε, η (IC50s=4-9 nM) and ζ (IC50=150 nM). Balanol also blocks the phosphorylation of cyclic AMP response element-binding protein (CREB) and myristoylated alanine-rich C kinase substrate (MARCKS). Balanol can be isolated from the fungus Verticillium balanoides[1][2].

  • CAS Number: 63590-19-2
  • MF: C28H26N2O10
  • MW: 550.51300
  • Catalog: PKC
  • Density: 1.62g/cm3
  • Boiling Point: 935.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 519.8ºC

Ingenol 3-mebutate

Ingenol Mebutate is an active ingredient in Euphorbia peplus, acts as a potent PKC modulator, with Kis of 0.3, 0.105, 0.162, 0.376, and 0.171 nM for PKC-α, PKC-β, PKC-γ, PKC-δ, and PKC-ε, respectively, and has antiinflammatory and antitumor activity.

  • CAS Number: 75567-37-2
  • MF: C25H34O6
  • MW: 430.534
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 576.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 191.4±23.6 °C

USP10 inhibitor Wu-5

USP10 inhibitor Wu-5 (Wu-5) is a novel small molecule USP10 inhibitor inducing the degradation of FLT3-mutated protein, directly interacts and inactivates USP10, the deubiquitinase for FLT3-ITD in vitro (IC50=8.3 uM) and in FLT3-ITD-positive AML cells.Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 uM, respectively.Wu-5 (1-10 μM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD.Combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins.

  • CAS Number: 2630378-05-9
  • MF: C15H13NO7S
  • MW: 351.329
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chaetocin

Chaetocin is a specific inhibitor of the histone methyltransferase (HMT) SU(VAR)3-9 with an IC50 of 0.6 μM for SU(VAR)3-9. It also inhibits thioredoxin reductase (TrxR) with an IC50 of 4 μM.

  • CAS Number: 28097-03-2
  • MF: C30H28N6O6S4
  • MW: 696.840
  • Catalog: Histone Methyltransferase
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Azacitidine (5-Azacytidine)

5-Azacytidine is a nucleoside analogue of cytidine that specifically inhibits DNA methylation by trapping DNA methyltransferases.

  • CAS Number: 320-67-2
  • MF: C8H12N4O5
  • MW: 244.205
  • Catalog: Autophagy
  • Density: 2.1±0.1 g/cm3
  • Boiling Point: 534.5±60.0 °C at 760 mmHg
  • Melting Point: 226-232 °C (dec.)(lit.)
  • Flash Point: 277.0±32.9 °C

Trichostatin A

Trichostatin A is a potent and specific inhibitor of HDAC class I/II, with an IC50 value of 1.8 nM for HDAC.

  • CAS Number: 58880-19-6
  • MF: C17H22N2O3
  • MW: 302.368
  • Catalog: HDAC
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 141-143ºC
  • Flash Point: N/A

Tankyrase-IN-5

Tankyrase-IN-5 (Compound 30f), an analogue of MSC2504877 (HY-123851), is a tankyrase TNKS1 and TNKS2 inhibitor with IC50s of 2.3 nM and 7.9 nM, respectively[1].

  • CAS Number: 1460285-69-1
  • MF: C17H18N2O2
  • MW: 282.34
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MT1

MT1 is a bivalent chemical probe of BET bromodomains, with an IC50 of 0.789 nM for BRD4(1)[1].

  • CAS Number: 2060573-82-0
  • MF: C54H66Cl2N10O9S2
  • MW: 1134.20
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A