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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Chonglou Saponin VII

Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia[1].

  • CAS Number: 68124-04-9
  • MF: C51H82O21
  • MW: 1031.184
  • Catalog: Bcl-2 Family
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ro 32-0432 hydrochloride

Ro 32-0432 hydrochloride is a potent, selective, ATP-competitive and orally active PKC inhibitor. The IC50 values of Ro 32-0432 hydrochloride for PKCα, PKCβI, PKCβII, PKCγ and PKCε are 9.3 nM, 28 nM, 30 nM, 36.5 nM and 108.3 nM, respectively. Ro 32-0432 hydrochloride is also a selective G protein-coupled receptor kinase 5 (GRK5) inhibitor. Ro 32-0432 hydrochloride prevents T-cell activation and has the potential for chronic inflammatory and autoimmune diseases research[1][2].

  • CAS Number: 1781828-85-0
  • MF: C28H29ClN4O2
  • MW: 489.01
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALK-IN-26

ALK-IN-26 is an ALK inhibitor with IC50 value of 7.0 μM for ALK tyrosine kinase. ALK-IN-26 has good pharmacokinetic properties and blood-brain barrier (BBB) permeability. ALK-IN-26 can induce apoptosis, autophagy and necrosis. ALK-IN-26 can be used in glioblastoma studies[1].

  • CAS Number: 2447607-85-2
  • MF: C24H23NO3S
  • MW: 405.51
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CDK/HDAC-IN-2

CDK/HDAC-IN-2 is a potent HDAC/CDK dual inhibitor with IC50 of 6.4, 0.25, 45, >1000, 8.63, 0.30, >1000 nM for HDAC1, HDAC2, HDAC3, HDAC6,8, CDK1, CDK2, CDK4,6,7, respectively. CDK/HDAC-IN-2 shows excellent antiproliferative activities. CDK/HDAC-IN-2 induces apoptosis and cell cycle arrest at G2/M phase. CDK/HDAC-IN-2 shows potent antitumor efficacy[1].

  • CAS Number: 2580938-58-3
  • MF: C25H20Cl2N6O3
  • MW: 523.37
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BET degrader-2

PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins with an IC50 value of 9.6 nM in cell growth inhibition in the RS4;11 cells and capable of achieving tumor regression.

  • CAS Number: 2093388-33-9
  • MF: C41H42N10O6
  • MW: 770.84
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Met/HDAC-IN-2

c-Met/HDAC-IN-2 is a highly potent c-Met and HDAC dual inhibitor with IC50s of 18.49 nM and 5.40 nM for HDAC1 and c-Met, respectively. c-Met/HDAC-IN-2 has antiproliferative activities against certain cancer cell lines. c-Met/HDAC-IN-2 can cause G2/M-phase arrest and induce apoptosis in HCT-116. c-Met/HDAC-IN-2 can be used for researching anti-cancer resistance[1].

  • CAS Number: 2740495-53-6
  • MF: C34H33N5O7
  • MW: 623.66
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ac-93253 iodide

AC-93253 is a selective, potent SIRT2 inhibitor. AC93253 can inhibit SIRT2 with an IC50 value of 6 μM. AC93253 can be used for the research of tumors[1].

  • CAS Number: 108527-83-9
  • MF: C23H25IN2S
  • MW: 488.42700
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SJ1461

SJ1461 is a potent and orally active BET inhibitor. SJ1461 inhibits BRD2 (BD1), and BRD2 (BD2), BRD4 (BD1), and BRD4 (BD2) with IC50 values of 1.6 nM, 0.1 nM, 6.5 nM, and 0.2 nM, respectively[1].

  • CAS Number: 2924546-70-1
  • MF: C21H18ClN7OS2
  • MW: 484.00
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OTS186935 trihydrochloride

OTS186935 trihydrochloride is a protein methyltransferase SUV39H2 inhibitor with an IC50 of 6.49 nM. OTS186935 trihydrochloride shows significant inhibition of tumor growth in mouse xenograft models without any detectable toxicity. OTS186935 trihydrochloride regulates the production of γ-H2AX in cancer cells[1].

  • CAS Number: 2093401-85-3
  • MF: C25H29Cl4N5O2
  • MW: 573.34
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT1-IN-1

PRMT1-IN-1 is a PRMT1 inhibitor.

  • CAS Number: 1025948-98-4
  • MF: C20H7Br6NO5
  • MW: 820.7
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FL-411

FL-411 is a potent and selective BRD4 inhibitor with an IC50 of 0.43±0.09 μM for BRD4(1).

  • CAS Number: 2118944-88-8
  • MF: C18H19N3O2S
  • MW: 341.43
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPQ

DPQ is a potent PARP-1 inhibitor. DPQ can reduce the N-methyl-d-aspartate (NMDA)-induced PARP activation, restoring ATP to near control levels and significantly attenuating neuronal injury in the severe NMDA exposure model. DPQ can be used for researching neuroprotection[1].

  • CAS Number: 129075-73-6
  • MF: C18H26N2O2
  • MW: 302.41
  • Catalog: PARP
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 528.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.6±30.1 °C

NI 42

NI-42 (compound 13-d), a structurally orthogonal chemical probe for the BRPFs, is a biased, potent inhibitor of the BRD of the BRPFs (IC50s of BRPF1/2/3=7.9/48/260 nM; Kds of BRPF1/2/3=40/210/ 940 nM) with excellent selectivity over nonclass IV BRD proteins[1].

  • CAS Number: 1884640-99-6
  • MF: C18H15N3O3S
  • MW: 353.40
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC 694623

NSC 694623 is a potent histone acetyltransferase (HAT) inhibitor with an IC50 value of 15.9 μM for recombinant HAT p300/CBP-associated factor (PCAF). NSC 694623 has antiproliferative activity against certain cancer cells. NSC 694623 can be used for researching anticancer[1].

  • CAS Number: 907957-34-0
  • MF: C16H16N2OS
  • MW: 284.38
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydro-5-azacytidine

Dihydro-5-azacytidine (DHAC), the nucleoside analog, is incorporated into DNA and inhibits DNA methylation. Dihydro-5-azacytidine has an antitumor activity[1][2].

  • CAS Number: 62488-57-7
  • MF: C8H14N4O5
  • MW: 246.221
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: 2.1±0.1 g/cm3
  • Boiling Point: 529.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.8ºC

PIN1 inhibitor 2

PIN1 inhibitor 2 (compound 12) is a potent PIN1 inhibitor. PIN1 inhibitor 2 shows antitumor activity with an IC50 of 9.55 µM for MCF7 cells. PIN1 inhibitor 2 has the potential for the research of breast cancer[1].

  • CAS Number: 2417101-28-9
  • MF: C16H21N3S2
  • MW: 319.49
  • Catalog: MicroRNA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP Inhibitor IX, EB-47

EB-47, a potent and selective PARP-1/ARTD-1 inhibitor with an IC50 value of 45 nM, shows modest potency against ARTD5 with an IC50 value of 410 nM. EB-47 mimics the substrate NAD+ and extends from the nicotinamide to the adenosine subsite[1].

  • CAS Number: 366454-36-6
  • MF: C24H27N9O6
  • MW: 537.52800
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OTS186935

OTS186935 is a protein methyltransferase SUV39H2 inhibitor with an IC50 of 6.49 nM[1].

  • CAS Number: 2093400-18-9
  • MF: C25H26ClN5O2
  • MW: 463.96
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D,L-erythro-Dihydrosphingosine

DL-erythro-Dihydrosphingosine is a potent inhibitor of PKC and phospholipase A2 (PLA2)[1][2].

  • CAS Number: 3102-56-5
  • MF: C18H39NO2
  • MW: 301.50800
  • Catalog: PKC
  • Density: 0.927g/cm3
  • Boiling Point: 446.2ºC at 760 mmHg
  • Melting Point: 70-72ºC
  • Flash Point: 223.7ºC

Curcumin

Curcumin is a natural phenolic compound with diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Curcumin is an inhibitor of p300 histone acetylatransferase ((HATs)) and also shows inhibitory effects on NF-κB and MAPKs.

  • CAS Number: 458-37-7
  • MF: C21H20O6
  • MW: 368.380
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 593.2±50.0 °C at 760 mmHg
  • Melting Point: 183 °C
  • Flash Point: 209.7±23.6 °C

GSK J5 HCl

GSK-J5 hydrochloride is a cell-permeable ester derivative of GSK J2 (HY-15648A), inactive. GSK-J5 hydrochloride is also an isomer of GSK-J4 (HY-15648B) and often used as a negative group[1].

  • CAS Number: 1797983-32-4
  • MF: C24H28ClN5O2
  • MW: 453.96
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRT3657

SRT3657 is a brain-permeable activator of SIRT1, with neuroprotective effect[1].

  • CAS Number: 1383551-17-4
  • MF: C40H54N8O6S
  • MW: 774.97
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

C646

C646 is a selective and competitive histone acetyltransferase p300 inhibitor with Ki of 400 nM, and is less potent for other acetyltransferases.

  • CAS Number: 328968-36-1
  • MF: C24H19N3O6
  • MW: 445.424
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 662.6±65.0 °C at 760 mmHg
  • Melting Point: 224-226℃
  • Flash Point: 354.5±34.3 °C

N-Hydroxy-N'-(4-iodophenyl)octanediamide

4-Iodo-SAHA (1k) is an orally active class I and class II histone deacetylase (HDAC) inhibitor with EC50s of 1.1, 0.95, 0.12, 0.24, 0.85 and 1.3 μM for Skbr3, HT29, U937, JA16 and HL60 cell lines, respectively. 4-Iodo-SAHA (1k) can be used for the research of cancer[1].

  • CAS Number: 1219807-87-0
  • MF: C14H19IN2O3
  • MW: 390.217
  • Catalog: HDAC
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Corin

Corin is a dual inhibitor of histone lysine specific demethylase (LSD1) and histone deacetylase (HDAC), with a Ki(inact) of 110 nM for LSD1 and an IC50 of 147 nM for HDAC1.

  • CAS Number: 1808113-09-8
  • MF: C26H28N4O2
  • MW: 428.53
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Menin-MLL inhibitor 19

Menin-MLL inhibitor 19, a potent exo-aza spiro inhibitor of menin-mll interaction, example A17, extracted from patent WO2019120209A1. Menin-MLL inhibitor 19 can be used for the reseaech of various diseases, such as cancer, myelodysplastic syndrome (MDS) and diabetes[1].

  • CAS Number: 2360487-93-8
  • MF: C30H34F3N7O4S
  • MW: 645.70
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNMT3A-IN-1

DNMT3A-IN-1 is a potent and selective DNMT3A inhibitor. DNMT3A-IN-1 shows inhibitor activities against DNMT3A with kI values range from 9.16-18.85 μM (AdoMet) and 11.37-23.34 μM (poly dI-dC) [1].

  • CAS Number: 1403598-56-0
  • MF: C30H38N6O4
  • MW: 546.66
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CUDC-907

Fimepinostat (CUDC-907) potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes with an IC50 of 19/54/39 nM and 1.7/5.0/1.8/2.8 nM for PI3Kα/PI3Kβ/PI3Kδ and HDAC1/HDAC2/HDAC3/HDAC10 , respectively.

  • CAS Number: 1339928-25-4
  • MF: C23H24N8O4S
  • MW: 508.553
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-fluoro-2-(4-methylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one acetate

Rucaparib (AG014699) acetate is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib acetate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib acetate has the potential for castration-resistant prostate cancer (CRPC) research[1][2][3][4].

  • CAS Number: 773059-23-7
  • MF: C21H22FN3O3
  • MW: 383.41600
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lestaurtinib

Lestaurtinib (CEP-701;KT-5555) is a multi-kinase inhibitor with potent activity against the Trk family of receptor tyrosine kinases. Lestaurtinib inhibits JAK2, FLT3 and TrkA with IC50s of 0.9, 3 and less than 25 nM, respectively.

  • CAS Number: 111358-88-4
  • MF: C26H21N3O4
  • MW: 439.463
  • Catalog: JAK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 723.0±60.0 °C at 760 mmHg
  • Melting Point: 215-220ºC
  • Flash Point: 391.0±32.9 °C