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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Tofacitinib (CP-690550) Citrate

Tofacitinib citrate is a JAK1/2/3 inhibitor with IC50s of 1, 20, and 112 nM, respectively.

  • CAS Number: 540737-29-9
  • MF: C22H28N6O8
  • MW: 504.493
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lumbokinase capsules

Lumbokinase capsules attenuates myocardial ischemia-reperfusion (I-R) injury through the activation of Sirt1 signaling, and thus enhances autophagic flux and reduces I-R-induced oxidative damage, inflammation and apoptosis[1].

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

Verminoside

Verminoside is an iridoid isolated from Kigelia africana, exhibits anti-inflammatory and remarkable antioxidant activity with a radical-scavenging activity of 2.5 μg/mL. The genotoxicity of Verminoside on human lymphocytes is associated with elevated levels of PARP-1 and p53 proteins[1][2][3].

  • CAS Number: 50932-19-9
  • MF: C24H28O13
  • MW: 492.473
  • Catalog: MDM-2/p53
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 739.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 253.2±26.4 °C

EZH2-​IN-​2

EZH2-IN-2 is a EZH2 inhibitor extracted from patent WO2018133795A1, Compound Example 69, with an IC50 of 64 nM. EZH2-IN-2 can be used for the research of cancer or precancerous condition related to EZH2 activity[1].

  • CAS Number: 2238821-31-1
  • MF: C36H46N6O3
  • MW: 610.79
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Buformin hydrochloride

Buformin hydrochloride (1-Butylbiguanide hydrochloride) is a potent and orally active biguanide antidiabetic agent, an AMPK activator. Buformin hydrochloride decreases hepatic gluconeogenesis and lowers blood glucose production in vivo. Buformin hydrochloride also has anti-cancer activities and is applied in cancer study (such as, cervical cancer and breast cancer, et al)[1].

  • CAS Number: 1190-53-0
  • MF: C6H16ClN5
  • MW: 193.67800
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: 322.7ºC at 760 mmHg
  • Melting Point: 174-177ºC
  • Flash Point: 148.9ºC

AMPK activator 12

AMPK activator 12 (compound 21) is a potent AMPK activator and GDF15 inducer. AMPK activator 12 increases GDF15 protein levels in human hepatic cells[1].

  • CAS Number: 431920-24-0
  • MF: C23H24BrNO2
  • MW: 426.35
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KPZ560

KPZ560 is a potent inhibitor of HDAC1 and HDAC2, with IC50s of 12 nM and 68 nM, respectively. KPZ560 can increase in the spine density of granule neuron dendrites of mice and inhibitor cell growth of breast cancer cell line MCF[1].

  • CAS Number: 2397562-43-3
  • MF: C26H21N5O3S2
  • MW: 515.61
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rucaparib camsylate

Rucaparib (AG014699) camsylate 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 camsylate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib camsylate has the potential for castration-resistant prostate cancer (CRPC) research[1][2][3][4].

  • CAS Number: 1327258-57-0
  • MF: C19H18FN3O.xC10H16O4S
  • MW:
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KAT modulator-1

KAT modulator-1 (Compound 3) is a KAT modulator. KAT modulator-1 can interact with p300 full-length but not with the catalytic domain. KAT modulator-1 can be used for epigenetics research[1].

  • CAS Number: 1314006-43-3
  • MF: C20H36O2
  • MW: 308.50
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PJ34

PJ34 is a potent specific inhibitor of PARPl/2 with IC50 of 110 nM and 86 nM, respectively.

  • CAS Number: 344458-19-1
  • MF: C17H17N3O2
  • MW: 295.336
  • Catalog: PARP
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 453.3±38.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 227.9±26.8 °C

RSC 133

RSC133 exhibits dual activity by inhibiting histone deacetylase and DNA methyltransferase. RSC133 effectively facilitates reprogramming of human somatic cells to pluripotent stem cells and supports the maintenance of an undifferentiated state of human pluripotent stem cells[1].

  • CAS Number: 1418131-46-0
  • MF: C18H15N3O2
  • MW: 305.331
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 653.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.1±31.5 °C

SB-284851-BT

SB-284851-BT is an inhibitor of BRD4/p38α/BRDT. SB-284851-BT inhibits BRD4-BD1 (IC50=1.7 µM), p38α (Kd=0.47 nM), BRDT (1) (IC50=18 µM) and BRD4 (1)(IC50=3.7 µM). SB-284851-BT reduces IL-8 production by inhibiting p38α, as well as inhibiting BRD4 to down-regulates c-Myc and NF-κB gene pathways in cancer. SB-284851-BT can combined with the bromine domain and extra terminal (BET)[1][2].

  • CAS Number: 219769-23-0
  • MF: C26H26FN5O
  • MW: 443.52
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ep300/CREBBP-IN-4

Ep300/CREBBP-IN-4 (Example 56) is a potent Ep300 and CREBBP inhibitor with IC50s of 0.024 and 0.064 μM, respectively. Ep300/CREBBP-IN-4 can be used for the research of cancer[1].

  • CAS Number: 2259641-42-2
  • MF: C23H22F3N5O3
  • MW: 473.45
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fasudil Hydrochloride Hydrate

Fasudil (HA-1077; AT877) hydrochloride semihydrate is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an Ki of 0.33 μM for ROCK1, IC50s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil hydrochloride semihydrate is also a potent Ca2+ channel antagonist and vasodilator[1][2][3].

  • CAS Number: 186694-02-0
  • MF: C28H38Cl2N6O5S2
  • MW: 673.67500
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OXFBD04

OXFBD04 is a potent and selective BRD4 inhibitor with an IC50 of 166 nM. OXFBD04 is a potent BET bromodomain ligand with additional modest affinity for the CREBBP bromodomain. OXFBD04 has anti-cancer activity[1].

  • CAS Number: 2231747-03-6
  • MF: C17H16N2O3
  • MW: 296.32
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A