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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Boc-Lys(Ac)-AMC

Boc-Lys(Ac)-AMC is a cell-permeable fluorometric HDAC substrate (Ex/Em = 355 nm/460 nm)[1][2].

  • CAS Number: 233691-67-3
  • MF: C23H31N3O6
  • MW: 445.50900
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nepodin

Nepodin (Musizin) is a quinone oxidoreductase (PfNDH2) inhibitor isolate from Rumex crispus[1].Nepodin (Musizin) stimulates the translocation of GLUT4 to the plasma membrane by activation of AMPK[2].Nepodin (Musizin) has antidiabetic and antimalarial activities.

  • CAS Number: 3785-24-8
  • MF: C13H12O3
  • MW: 216.233
  • Catalog: AMPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 413.2±40.0 °C at 760 mmHg
  • Melting Point: 165-166℃ (methanol )
  • Flash Point: 217.8±23.8 °C

WM-586

WM-586 is a covalent WDR5 inhibitor that disrupts the binding of WDR5 to MYC. WM-586 specifically decreases cellular WDR5 and MYC interaction with the IC50 of 101 nM in HTRF assay[1].

  • CAS Number: 2894832-05-2
  • MF: C20H20F3N5O3S
  • MW: 467.46
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PLSRTLSVAAKK

[Ala9,10, Lys11,12] Glycogen Synthase (1-12) is a selective substrate for phosphorylation by protein kinase C (PKC). [Ala9,10, Lys11,12] Glycogen Synthase (1-12) can be used to determine the activity of protein kinase C[1].

  • CAS Number: 105802-84-4
  • MF: C56H103N17O16
  • MW: 1270.52000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

(Rac)-Ruxolitinib D9

(Rac)-Ruxolitinib D9 ((Rac)-INCB18424 D9) is the deuterium labeled (Rac)-Ruxolitinib. (Rac)-Ruxolitinib is a JAK2 inhibitor[1].

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

PDAT

PDAT is a noncompetitive Indolethylamine N-methyltransferase inhibitor.

  • CAS Number: 1226213-83-7
  • MF: C15H23N3
  • MW: 245.36
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

EZH2-IN-4

EZH2-IN-4 is an orally active, potent EZH2 inhibitor with IC50s of 0.923 nM and 2.65 nM against wild type (WT) 5-membered (5-mer) EZH2 and mutant 5-mer EZH2, respectively. EZH2-IN-4 has anti-cancer activity[1].

  • CAS Number: 2088132-99-2
  • MF:
  • MW:
  • Catalog: Histone Methyltransferase
  • 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

BAY 598

BAY-598 is selective small molecule inhibitor of SMYD2 .

  • CAS Number: 1906919-67-2
  • MF: C22H20Cl2F2N6O3
  • MW: 525.34
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brevilin A

Brevilin A is a sesquiterpene lactone isolated from Centipeda minima with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 µM) in Cancer Cells. Brevilin A induces apoptosis and autophagy via mitochondrial pathway and PI3K/AKT/mTOR inactivation in colon adenocarcinoma cell CT26[1][2].

  • CAS Number: 16503-32-5
  • MF: C20H26O5
  • MW: 346.417
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 494.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.0±28.8 °C

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

Xanthoangelol

Xanthoangelol, extracted from Angelica keiskei, suppresses obesity-induced inflammatory responses. Xanthoangelol possesses antibacterial activity[1][2]. Xanthoangelol and inhibits monoamine oxidases[3]. Xanthoangelol induces apoptosis in neuroblastoma and leukemia cells[4].

  • CAS Number: 62949-76-2
  • MF: C25H28O4
  • MW: 392.48700
  • Catalog: Bacterial
  • Density: 1.165g/cm3
  • Boiling Point: 605.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 334.2ºC