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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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

pociredir

Pociredir (FTX-6058) is a potent, selective and orally active small-molecule inhibitor of embryonic ectoderm development (EED) with KD value of 0.163 nM. Pociredir (FTX-6058) can be used for the research of inflammatory or hemoglobinopathies, such as sickle cell disease (SCD) [1][2].

  • CAS Number: 2490674-02-5
  • MF: C22H18FN5O2
  • MW: 403.41
  • Catalog: Histone Methyltransferase
  • 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

PS-432

PS-432 is an allosteric inhibitor of PKCι and PKCζ with IC50 of 16.9 and 18.5 uM, respectively; has no inhibitory activity against PKCα, PKCβ, PKCδ and PKCθ nor the activity of related kinases such as PDK1, PKB/Akt, RSK1, MSK1 and Aurora A; inhibits the proliferation of the lung cancer cell lines A549 (IC50=14.8 ± 4.2 uM) and A427 (IC50=10.4± 0.3 uM) as well as androgen-independent prostate cancer cell line DU145 (IC50 = 20.8 ± 9.0 uM); well tolerated in vivo.

  • CAS Number: 2083630-26-4
  • MF: C25H19ClN2O5S
  • MW: 494.947
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 662.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.5±34.3 °C

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

CRA-026440 hydrochloride

CRA-026440 hydrochloride is a potent, broad-spectrum HDAC (HDAC) inhibitor. The Ki values against recombinant HDAC isoenzymes HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM respectively. CRA-026440 hydrochloride shows antitumor and antiangiogenic activities[1].

  • CAS Number: 847459-98-7
  • MF: C23H25ClN4O4
  • MW: 456.92
  • Catalog: Apoptosis
  • 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

DCLX069

DCLX069 is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC50 value of 17.9 µM. DCLX069 shows less active against PRMT4 and PRMT6. DCLX069 has anticancer effects[1].

  • CAS Number: 792946-69-1
  • MF: C20H25N3O2
  • MW: 339.431
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 515.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.8±30.1 °C

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

JAK1/TYK2-IN-1

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 (IC50 = 29 and 41 nM respectively).

  • CAS Number: 1883300-48-8
  • MF: C18H20F3N7O
  • MW: 407.39
  • Catalog: JAK
  • 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

AZ506

AZ506 is a potent SMYD2 inhibitor with an IC50 of 17 nM. AZ506 inhibits SMYD2 methyltransferase activity in cells, leading to a decrease in the SMYD2-mediated methylation signal.

  • CAS Number: 2043321-54-4
  • MF: C33H40N6O
  • MW: 536.71
  • Catalog: Histone Methyltransferase
  • 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

Phenanthridin-6(5H)-one

6(5H)-Phenanthridinone is a potent PARP-1 inhibitor and immunomodulator. 6(5H)-Phenanthridinone inhibits cell proliferation and can be used in cancer research[1].

  • CAS Number: 1015-89-0
  • MF: C13H9NO
  • MW: 195.22
  • Catalog: PARP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 274.8±7.0 °C at 760 mmHg
  • Melting Point: 290-292 °C(lit.)
  • Flash Point: 158.7±3.1 °C

EPZ011989

EPZ011989 is a potent, selective orally bioavailable EZH2 inhibitor with Ki < 3 nM for EZH2 wt and EZH2 Y646; 15-fold selectivity over EZH1 and >3000-fold selectivity over other HMTase.IC50 value: < 3 nM ( Ki for wt EZH2, EZH2 Y646)Target: EZH2 inhibitorIn vitro: EPZ011989 is also a specific EZH2 inhibitor with a >15-fold selectivity over EZH1 and >3000-fold selectivity relative to the Ki of 20 other histone methyltransferases (HMTs) tested. EPZ011989 also exhibits metabolic stability. Furthermore, EPZ011989 reduces cellular H3K27 methylation in the Y641F, mutant-bearing human lymphoma cell line, WSU-DLCL2, with an IC50 below 100 nM. This functional response translates to activity in a long-term proliferation assay where EPZ011989 demonstrates an average lowest cytotoxic concentration (LCC) in WSU-DLCL2 cells of 208 nM. In vivo: The LCC parameter, when corrected for plasma protein-binding, predicts an efficacious plasma level in mouse for EPZ011989 of 158 ng/mL. The pharmacokinetics in SCID mice following oral administration of 125, 250, 500, and 1000 mg/kg indicated that the 1000 mg/kg dose provided coverage over the LCC for 24 h, while the 250 and 500 mg/kg doses provided coverage over this value for approximately 8 h. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma.

  • CAS Number: 1598383-40-4
  • MF: C35H51N5O4
  • MW: 605.810
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 756.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 411.4±32.9 °C

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

OUL 35

OUL35 (NSC39047) is a potent and selective inhibitor of ARTD10 (PARP-10), with an IC50 of 329 nM[1].

  • CAS Number: 6336-34-1
  • MF: C14H12N2O3
  • MW: 256.25700
  • Catalog: PARP
  • Density: 1.298g/cm3
  • Boiling Point: 488.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 257.9ºC

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

6-Gingerol

[6]-Gingerol is an active compound isolated from Ginger (Zingiber officinale Rosc), exhibits a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation.

  • CAS Number: 23513-14-6
  • MF: C17H26O4
  • MW: 294.386
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 453.0±35.0 °C at 760 mmHg
  • Melting Point: 30 - 32ºC
  • Flash Point: 159.0±19.4 °C

PARP1-IN-7

PARP1-IN-7 is an inhibitor of poly(ADP-ribose) polymerase-1 (PARP1) as an anticancer agent.

  • CAS Number: 2084112-75-2
  • MF: C24H23N5O
  • MW: 397.47
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Tozasertib

Tozasertib is the inhibitor of Aurora A/B/C kinases with Kis of 0.6, 18, 4.6 nM, respectively.

  • CAS Number: 639089-54-6
  • MF: C23H28N8OS
  • MW: 464.586
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

E67-2

E67-2 is a potent and selective inhibitor of H3K9 Jumonji demethylase KIAA1718 (KDM7A) with IC50 of 3.4 uM; selectively inhibits H3K9 Jumonji demethylase over H3K9 methyltransferase as well as H3K4 demethylase, has low cytotoxicity.

  • CAS Number: 1364914-62-4
  • MF: C21H36N6O2
  • MW: 404.559
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-Deoxyisojacareubin

6-Deoxyisojacareubin is a PKC inhibitor that inhibits the proliferation of QGY-7703 cells in a concentration-dependent manner. 6-Deoxyisojacareubin is also a natural product that can be obtained from Garcinia nervosa. 6-Deoxyisojacareubin can be used in cancer research[1].

  • CAS Number: 26486-92-0
  • MF: C18H14O5
  • MW: 310.30
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A