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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QC6352

QC6352 is a potent KDM4C inhibitor with an IC50 of 35 nM.

  • CAS Number: 1851373-36-8
  • MF: C24H25N3O2
  • MW: 387.47
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Urolithin B

Urolithin B is one of the gut microbial metabolites of ellagitannins, and has anti-inflammatory and antioxidant effects. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass[1][2].

  • CAS Number: 1139-83-9
  • MF: C13H8O3
  • MW: 212.20100
  • Catalog: AMPK
  • Density: 1.395g/cm3
  • Boiling Point: 432.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 196.6ºC

DC-CPin7

DC-CPin7 is a potent inhibitor of CREB-binding protein (CBP) bromodomain with an IC50 of 2.5 μM[1].

  • CAS Number: 893781-17-4
  • MF: C19H22N2O5
  • MW: 358.39
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Seclidemstat mesylate

Seclidemstat (SP-2577) mesylate is a potent noncompetitive and reversible KDM1A (LSD1) inhibitor (Ki=31 nM, IC50=13 nM). Seclidemstat mesylate promotes antitumor immunity in switch/sucrose nonfermentable (SWI/SNF) complex mutated ovarian cancer, as well as inhibit virus production, viral DNA replication, and late gene expression. Seclidemstat mesylate can be used for the research of Ewing Sarcoma[1][2].

  • CAS Number: 2044953-70-8
  • MF: C21H27ClN4O7S2
  • MW: 547.04
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-4827 tosylate

Niraparib tosylate (MK-4827 tosylate) is an excellent PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively.

  • CAS Number: 1038915-73-9
  • MF: C26H28N4O4S
  • MW: 492.59000
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ADTL-SA1215

ADTL-SA1215 is a first-in-class specific small-molecule activator of SIRT3 that modulates autophagy in triple negative breast cancer.

  • CAS Number: 782387-91-1
  • MF: C26H29I2NO3
  • MW: 657.32
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-8722

MK8722 is a potent and systemic pan-AMPK activator.

  • CAS Number: 1394371-71-1
  • MF: C24H20ClN3O4
  • MW: 449.89
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-[4-(1,3-Benzodioxol-5-ylmethyl)-1-piperazinyl]pyrimidine hydrochloride (1:1)

Piribedil dihydrochloride is a potent and orally active dopamine D2 and dopamine D3 agonist. Piribedil dihydrochloride is also a α2-adrenoceptors antagonist. Piribedil dihydrochloride can inhibit MLL1 methyltransferase activity (EC50: 0.18 μM). Piribedil dihydrochloride has the potential for the research of parkinson's disease, circulatory disorders, cancers[1][2][3][4].

  • CAS Number: 1451048-94-4
  • MF: C16H19ClN4O2
  • MW: 334.801
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPI-0610 carboxylic acid

CPI-0610 carboxylic acid is a ligand for target protein for protact. CPI-0610 carboxylic acid is a potent bromodomain and extra-terminal (BET) protein inhibitor in the therapy of multiple myeloma[1].

  • CAS Number: 1380089-81-5
  • MF: C20H15ClN2O3
  • MW: 366.80
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EB-3D

EB-3D is a novel potent and selective choline kinase ChoKα inhibitor with IC50 of 1.0 uM (purified ChoKα1), strongly impairs cell proliferation in a variety of different cancer cell lines; demonstrates in vitro antiproliferative effects against HeLa (IC50=79 nM), RS4,11 (IC50=45 nM), A549 (IC50=27 nM) and MDA-MB-231 (IC50=100 nM); displays excellent antiproliferative activity against a wide cohort of T-leukemic cell lines with GI50 of 0.9 nM (MOLT-16 cell)-479 nM (CCRF-CEM), reduces the intracellular pool of PCho, but also inhibits the synthesis of choline-containing lipids; induces G0/G1 arrest that lead to apoptosis in leukemia cell lines; affects AMPK-mTOR signaling pathway, synergizes with both dexamethasone and L-asparaginase.

  • CAS Number: 1839150-63-8
  • MF: C30H36Br2N4O2
  • MW: 644.452
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CMPD101

CMPD101, is a novel membrane-permeable, small-molecule inhibitor of both GRK2 and GRK3 with IC50s of 18 nM and 5.4 nM. CMPD101 also inhibits ROCK-2 and PKCα (IC50s=1.4 μM and 8.1 μM, respectively)[1].

  • CAS Number: 865608-11-3
  • MF: C24H21F3N6O
  • MW: 466.458
  • Catalog: ROCK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dBET6

dBET6 is a highly potent, selective and cell-permeable degrader of BET based on PROTAC, with an IC50 of 14 nM, and has antitumor activity.

  • CAS Number: 1950634-92-0
  • MF: C42H45ClN8O7S
  • MW: 841.37
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CSV0C018875

CSV0C018875 is a quinoline-based EHMT2/G9a inhibitor. CSV0C018875 exhibits lesser cytotoxicity than BIX-01294[1].

  • CAS Number: 442150-41-6
  • MF: C18H17ClN2O
  • MW: 312.79
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Menin-MLL inhibitor 24

Menin-MLL inhibitor 24 (compound A) is a menin-mixed-lineage leukemia 1 (menin-MLL) inhibitor. Menin-MLL inhibitor 24 can be used for the research of cancer[1].

  • CAS Number: 2654081-35-1
  • MF: C32H50FN7O3
  • MW: 599.78
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Windorphen

Windorphen is a Wnt/β-catenin signal inhibitor that specifically targets the function of the c-terminal transactivation domain of β-catenin-1 but not β-catenin-2. Windorphen selectively targets p300, disrupting the association of the mammalian β-catenin with p300 but not CBP[1].

  • CAS Number: 19881-70-0
  • MF: C17H15ClO3
  • MW: 302.75
  • Catalog: Histone Acetyltransferase
  • Density: 1.198g/cm3
  • Boiling Point: 468.1ºC at 760mmHg
  • Melting Point: 160-163ºC
  • Flash Point: 184.7ºC

ZEN-3862

ZEN-3862 is a BET inhibitor with IC50s of 0.16 and 0.13 μM for BRD4(BD1) and BRD4(BD2) , respectively. ZEN-3862 can be used to form PROTACs to induce degradation of BRD4[1].

  • CAS Number: 1952264-33-3
  • MF: C19H17FN2O3
  • MW: 340.35
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WM-662

WM-662 is a WDR5-MYC interaction inhibitor, with an IC50 of 18 μM. WM-662 has potential for the research of cancer, aging, and neurodegenerative disorders[1].

  • CAS Number: 1308257-47-7
  • MF: C19H18ClN5O4
  • MW: 415.83
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thi-DPPY

Thi-DPPY (compound 8e) is a potent and orally active JAK3 inhibitor with IC50 values of 62.4, 1.38 nM for BTK, JAK, respectively. Thi-DPPY shows anti-proliferative activity against HBE cells. Thi-DPPY shows anti-inflammatory activity in vivo. Thi-DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].

  • CAS Number: 2307699-34-7
  • MF: C28H28ClN5O4S
  • MW: 566.07
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Y08284

Y08284 is a potent, selective, oral active CBP bromodomain inhibitor with an IC50 of 4.21 nM. Y08284 suppresses the proliferation of prostate cancer cell lines LNCaP, C4-2B, and 22Rv1. Antitumor activity[1].

  • CAS Number: 2688745-47-1
  • MF: C26H25FN4O4
  • MW: 476.50
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Biotinylated-JQ1

Biotinylated-JQ1 (Biotin-JQ1) is a biotinylated derivative of JQ1 with high affinity for the bromodomain of BRD4. Biotinylated-JQ1 inhibits MM1.S multiple myeloma cells proliferation with the EC50 of 0.4 μM[1].

  • CAS Number: 1635437-52-3
  • MF: C39H53ClN8O6S2
  • MW: 829.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-59

HDAC-IN-59 (compound 13a) is a potent histone deacetylase (HDAC) inhibitor. HDAC-IN-59 can promote the intracellular generation of ROS, cause DNA damage, block the cell cycle at G2/M phase, and activate the mitochondria-related apoptotic pathway to induce cell apoptosis[1].

  • CAS Number: 2944459-43-0
  • MF: C20H25NO7
  • MW: 391.42
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EZH2-IN-9

EZH2-IN-9 is a potent inhibitor of EZH2. EZH2 overexpression or mutations in the SET region (Y641F, Y641N, A687V, A677G point mutations) all lead to abnormal elevation of H3K27me3 and promote the growth and development of many types of tumors, such as breast cancer, prostate cancer, leukemia, etc. EZH2-IN-9 has the potential for the research of cancer diseases (extracted from patent WO2021180235A1, compound 17)[1].

  • CAS Number: 2700897-24-9
  • MF: C28H32ClF2N3O5S
  • MW: 596.09
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP1-IN-10

PARP1-IN-10 (compound 12c) is a no-cytotoxicity and potent PARP1 inhibitor with an IC50 value of 50.62 nM in vitro. PARP1-IN-10 causes cell cycle arrest at G2/M phase and apoptosis, and enhances the cytotoxicity of temozolomide (TMZ) [1].

  • CAS Number: 2494001-21-5
  • MF: C20H23N3O5
  • MW: 385.41
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PS315

PS315, a derivative of PS48 (HY-15967), is an allosteric PKC inhibitor by binding to the PIF-pocket of aPKC and inducing a displacement of the active site residue Lys111. PS315 inhibits the full-length and catalytic domain constructs of PKCζ (IC50=10 μM) and PKCη (IC50=30 μM). PS315 has anti-cancer activity[1].

  • CAS Number: 1221964-50-6
  • MF: C23H19ClO2
  • MW: 362.85
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6-IN-11

HDAC6-IN-11 (Compound 9) is a selective HDAC6 inhibitor with the IC50 value of 20.7 nM. HDAC6-IN-11 has more than 300-fold selectivity over HDAC other isoforms. HDAC6-IN-11 shows anti-proliferative activities against cancer cells[1].

  • CAS Number: 2409072-27-9
  • MF: C19H16N2O4
  • MW: 336.34
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LFM-A13

LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC50s of 2.5 μM, 10 μM and 61 μM. LFM-A13 has antiproliferative activity and anticancer activity. LFM-A13 can be used in cancer-related research[1][3][4]

  • CAS Number: 62004-35-7
  • MF: C11H8Br2N2O2
  • MW: 360.00
  • Catalog: Polo-like Kinase (PLK)
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 487.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.9±28.7 °C

GSK690

GSK 690 is a reversible inhibitor of lysine specific demethylase 1 (LSD1), with a Kd value of 9 nM and a biochemical IC50 of 37 nM.

  • CAS Number: 2101305-84-2
  • MF: C24H23N3O
  • MW: 369.459
  • Catalog: Histone Demethylase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 530.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.6±30.1 °C

EPZ004777 (hydrochloride)

EPZ004777 hydrochloride is a potent, selective DOT1L inhibitor with IC50 of 0.4 nM.

  • CAS Number: 1380316-03-9
  • MF: C28H42ClN7O4
  • MW: 576.13100
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSD3-IN-1

NSD3-IN-1 (compound B1) is an inhibitor of histone methyltransferase NSD3 with an IC50 value of 28.58 μM[1].

  • CAS Number: 347340-51-6
  • MF: C13H13N5OS
  • MW: 287.34
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EZH2-IN-3

EZH2-IN-3 is a highly selective small molecule inhibitor of EZH2 and EZH1 with IC50 of 21/197/213 nM for wt EZH2/EZH2 Y641N/wt EZH1 respectively; suppresses global histone H3-lysine 27 methylation and cause selective proliferation defects.

  • CAS Number: 1377997-28-8
  • MF: C27H28ClN5O2
  • MW: 489.996
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 666.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 356.8±31.5 °C