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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GSK-3β inhibitor 13

GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease[1].

  • CAS Number: 2227316-74-5
  • MF: C23H22N6O2
  • MW: 414.46
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CTPB

CTPB is a good activator of p300 histone acetyl transferase (HAT) enzyme[1].

  • CAS Number: 586976-24-1
  • MF: C31H43ClF3NO2
  • MW: 554.12700
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

G244-LM

G244-LM is a potent and specific inhibitor of tankyrase 1/2 that inhibits Wnt signaling[1].

  • CAS Number: 1563007-08-8
  • MF: C18H22N4O3S2
  • MW: 406.522
  • Catalog: PARP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC 926 hydrochloride

UNC926 hydrochloride is a methyl-lysine (Kme) reader domain inhibitor that inhibits L3MBTL1 with an IC50 of 3.9 μM[1].

  • CAS Number: 1782573-49-2
  • MF: C16H22BrClN2O
  • MW: 373.72
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-375

GNE-375 is a potent, selective BRD9 inhibitor with IC50 of 5 nM, displays >480-fold selectivity over BRD4, CECR2, and TAF1; decreases BRD9 binding to chromatin, and decreases expression of ALDH1A1, a gene previously shown to be important in drug tolerance; shows remarkable potency in preventing the emergence of a drug tolerant population in EGFR mutant PC9 cells treated with EGFR inhibitors.

  • CAS Number: 1926989-06-1
  • MF: C25H29N3O5
  • MW: 451.523
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

QCA570

QCA570 is a potent BET degrader based on PROTAC, with an IC50 of 10 nM for BRD4 BD1 Protein.

  • CAS Number: 2207569-08-0
  • MF: C39H33N7O4S
  • MW: 695.798
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NVP-BSK805 trihydrochloride

NVP-BSK805 trihydrochloride trihydrochloride is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively[1].

  • CAS Number: 2320258-95-3
  • MF: C27H31Cl3F2N6O
  • MW: 599.93
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protein Kinase C (660-673)

Protein Kinase C (660-673) (PKC βII (660-673)) is the PKC βII V5 peptide with RACK1-binding affinity[1].

  • CAS Number: 149839-94-1
  • MF: C74H115N17O23
  • MW: 1610.81
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3-IN-6

JAK3-IN-6 is a potent, selective irreversible Janus Associated Kinase 3 (JAK3) inhibitor, with an IC50 of 0.15 nM.

  • CAS Number: 1443235-95-7
  • MF: C19H18N4O3
  • MW: 350.37
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acadesine (AICAR)

AICAR is a cell-permeable AMP-activated protein kinase (AMPK) activator.

  • CAS Number: 2627-69-2
  • MF: C9H14N4O5
  • MW: 258.231
  • Catalog: Autophagy
  • Density: 2.1±0.1 g/cm3
  • Boiling Point: 726.3±60.0 °C at 760 mmHg
  • Melting Point: 214-215 °C
  • Flash Point: 393.1±32.9 °C

Cerdulatinib hydrochloride

Cerdulatinib hydrochloride (PRT062070) is a selective, oral active and reversible ATP-competitive inhibitor of dual SYK and JAK, with the IC50s of 32 nM, 0.5 nM, 12 nM, 6 nM and 8 nM for SYK and Tyk2, JAK1, 2, 3, respectively. Cerdulatinib hydrochloride could be used to research autoimmune disease and B-cell malignancies[1][2].

  • CAS Number: 1369761-01-2
  • MF: C20H28ClN7O3S
  • MW: 481.999
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(2-Propyn-1-yl)octanoic acid

2-Hexyl-4-pentynoic acid ((±)-2-Hexyl-4-pentynoic acid), valproic acid (VPA) derivative, exhibits potential roles of HDAC inhibition (IC50=13 µM) and HSP70 induction. Potent neuroprotective effects. 2-Hexyl-4-pentynoic acid causes histone hyperacetylation and protect against glutamate-induced excitotoxicity in cultured neurons[1].

  • CAS Number: 96017-59-3
  • MF: C11H18O2
  • MW: 182.259
  • Catalog: HDAC
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 287.1±23.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 138.7±17.3 °C

DL-Sulforaphane

Sulforaphane is an isothiocyanate present naturally in widely consumed vegetables; has shown anticancer and cardioprotective activities.

  • CAS Number: 4478-93-7
  • MF: C6H11NOS2
  • MW: 177.288
  • Catalog: HDAC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 368.2±25.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 176.5±23.2 °C

Lerzeparib

Lerzeparib is an (ADP-ribose) polymerase (PARP) inhibitor, with antineoplastic activity[1].

  • CAS Number: 2459693-01-5
  • MF: C21H20FN3O2
  • MW: 365.40
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LRRK2/NUAK1/TYK2-IN-1

LRRK2/NUAK1/TYK2-IN-1 (conpound 226) shows inhibitory activity toward LRRK2 (Wt), LRRK2 (G2019), TYK2 and NUAK1, with IC50 values lower than 10 nM. LRRK2/NUAK1/TYK2-IN-1 can be used for autoimmune disease research[1].

  • CAS Number: 2629192-96-5
  • MF: C20H11F3N6
  • MW: 392.34
  • Catalog: LRRK2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET-IN-12

BET-IN-12 is an orally avtive inhibitor of bromodomain and extra-terminal (BET) with an IC50 of 0.9 nM for BRD4[1].

  • CAS Number: 1800343-11-6
  • MF: C30H29D3FN5O2
  • MW: 516.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS-1020

MS-1020 is a potent and ATP-competitive JAK3 inhibitor. MS-1020 inhibits JAK3/STAT signaling and induces apoptosis. MS-1020 promotes cell death. MS-1020 decreases the expression of tyrosine phosphorylated STAT3 levels. MS-1020 has the potential for the research of cancers harboring aberrant JAK3 signaling[1].

  • CAS Number: 1255516-86-9
  • MF: C21H18N2O3
  • MW: 346.379
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 711.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 383.9±32.9 °C

ZL0454

ZL0454 is a potent and selective Bromodomain-containing protein 4 (BRD4) inhibitor with an IC50 of 49 and 32 nM for BD1 and BD2.

  • CAS Number: 2229042-77-5
  • MF: C18H22N4O3S
  • MW: 374.46
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NI-57

NI-57 is an inhibitor of bromodomain and plant homeodomain finger-containing (BRPF) famlily of proteins, with IC50s of 3.1, 46 and 140 nM for BRPF1, BRPF2 (BRD1) and BRPF3, respectively.

  • CAS Number: 1883548-89-7
  • MF: C19H17N3O4S
  • MW: 383.42
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT9283

AT9283 is a multitargeted kinase inhibitor which potently inhibits aurora kinase A/B, JAK2/3 (IC50=1.2 nM, 1.1 nM).

  • CAS Number: 896466-04-9
  • MF: C19H23N7O2
  • MW: 381.432
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KDM2B-IN-4

KDM2B-IN-4 is a histone demethylase KDM2B inhibitor extracted from patent WO2016112284A1, compound 182b. KDM2B-IN-4 can be used for the research of cancer[1].

  • CAS Number: 1966933-85-6
  • MF: C24H28N2O2
  • MW: 376.49
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E-7386

E-7386 is an orally active CBP/beta-catenin modulator.

  • CAS Number: 1799824-08-0
  • MF: C39H48FN9O4
  • MW: 725.85
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD7-IN-1 free base

BRD7-IN-1 free base, a modified derivative of BI7273 (BRD7/9 inhibitor), binds to a VHL ligand via a linker to form a PROTAC VZ185 (VZ185 against BRD7/9 with DC50s of 4.5 and 1.8 nM, respectively)[1].

  • CAS Number: 2305379-66-0
  • MF: C22H26N4O3
  • MW: 394.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AICAR phosphate

AICAR phosphate is an activator of AMP-activated protein kinase (AMPK), down-regulates the insulin receptor expression in HepG2 cells.

  • CAS Number: 681006-28-0
  • MF: C9H17N4O9P
  • MW: 356.23
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T-3775440 hydrochloride

T-3775440 (hydrochloride) is an irreversible lysine-specific histone demethylase (LSD1) inhibitor with an IC50 value of 2.1 nM.

  • CAS Number: 1422535-52-1
  • MF: C18H23ClN4O
  • MW: 346.85
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6-IN-4

HDAC6-IN-4 (C10) is a potent, orally active and highly selective HDAC6 inhibitor with an IC50 value of 23 nM. HDAC6-IN-4 induces cancer cells apoptosis and shows significant antitumor efficacy, without obvious toxicity[1].

  • CAS Number: 2709103-20-6
  • MF: C30H38N2O5
  • MW: 506.63
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CM-579

CM-579 is a first-in-class reversible, dual inhibitor of G9a and DNMT, with IC50 values of 16 nM, 32 nM for G9a and DNMT, respectively. Has potent in vitro cellular activity in a wide range of cancer cells[1].

  • CAS Number: 1846570-40-8
  • MF: C29H40N4O3
  • MW: 492.65
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MM-102

MM-102 is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM with an estimated Ki < 1 nM in WDR5 binding assay, which is >200 times more potent than the ARA peptide.IC50 value: 2.4 nMTarget: MLLin vitro: MM-102 inhibits MLL1 methyltransferase activity and MLL-1-induced HoxA9 and Meis-1 gene expression in leukemia cells expressing the MLL1-AF9 fusion gene. Also inhibits cell growth and induces apoptosis in leukemia cells harbouring MLL1 fusion proteins. MM-102, with the highest binding affinities to WDR5, also show the most potent inhibitory activity in the HMT assay with IC50 = 0.4-0.9 μM. MM-102 dose-dependently inhibits cell growth in the MV4;11 and KOPN8 leukemia cell lines, which carry MLL1-AF4 and MLL1-ENL fusion proteins, respectively. MM-102 has IC50 = 25 μM in both cell lines and completely inhibits cell growth in these cell lines at 75 μM. MM-102 effectively and selectively inhibits cell growth and induces apoptosis in leukemia cells harboring MLL1 fusion proteins and has minimal effect in leukemia cells with wild-type MLL1 protein.[1]

  • CAS Number: 1417329-24-8
  • MF: C35H49F2N7O4
  • MW: 669.80500
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MM-102 TFA

MM-102 (HMTase Inhibitor IX) TFA is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM with an estimated Ki < 1 nM in WDR5 binding assay, which is >200 times more potent than the ARA peptide.

  • CAS Number: 1883545-52-5
  • MF: C37H50F5N7O6
  • MW: 783.83
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-620223

A-620223 (succinate) (ABT-472) is an orally available poly(ADP-ribose) polymerase (PARP) inhibitor. A-620223 (succinate) (ABT-472) exhibits very good potency against the PARP-1 enzyme with a Ki value of 8 nM and an EC50 value of 3 nM in whole cell assay, making it useful in cancer research[1].

  • CAS Number: 943650-25-7
  • MF: C20H28N4O5
  • MW: 404.46000
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A