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.


Anti-infection >
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GSK9311 hydrochloride

GSK9311 hydrochloride, a less active analogue of GSK6853, can be used as a negative control. GSK9311 hydrochloride inhibits BRPF bromodomain with pIC50 values of 6.0 and 4.3 for BRPF1 and BRPF2, respectively[1].

  • CAS Number: 2253733-09-2
  • MF: C24H32ClN5O3
  • MW: 474.00
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

I-BET 151 dihydrochloride

I-BET151 dihydrochloride (GSK1210151A dihydrochloride) is a BET bromodomain inhibitor which inhibits BRD4, BRD2, and BRD3 with pIC50 of 6.1, 6.3, and 6.6, respectively[1][2].

  • CAS Number: 1883545-47-8
  • MF: C23H23Cl2N5O3
  • MW: 488.366
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS HDAC6 20b

TCS HDAC6 20b is a HDAC6-selective inhibitor. TCS HDAC6 20b blocks the growth of estrogen receptor α-positive breast cancer MCF-7 cells[1].

  • CAS Number: 956154-63-5
  • MF: C26H44N2O4S
  • MW: 480.704
  • Catalog: HDAC
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 631.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 335.6±31.5 °C

Pep2m, myristoylated

Pep2m, myristoylated (Myr-Pep2m) is a cell-permeable peptide. Pep2m, myristoylated can disrupt the protein kinase ζ (PKMζ) downstream targets, N-ethylmaleimide-sensitive factor/glutamate receptor subunit 2 (NSF/GluR2) interactions. PKMζ is an autonomously active isozyme of protein kinase C (PKC)[1][2].

  • CAS Number: 1423381-07-0
  • MF: C63H118N18O14S
  • MW: 1383.788
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ac-Lys-AMC

Ac-Lys-AMC (Hexanamide), also termed MAL, is a fluorescent substrate for histone deacetylase HDACs[1].

  • CAS Number: 156661-42-6
  • MF: C18H23N3O4
  • MW: 345.39300
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Valproic acid

Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.

  • CAS Number: 99-66-1
  • MF: C8H16O2
  • MW: 144.211
  • Catalog: Apoptosis
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 220.0±0.0 °C at 760 mmHg
  • Melting Point: 120 - 130ºC
  • Flash Point: 111.1±0.0 °C

EPZ019997

GSK3368715 dihydrochloride (EPZ019997 dihydrochloride) is an orally active, reversible, and S-adenosyl-L-methionine (SAM) uncompetitive type I protein arginine methyltransferases (PRMTs) inhibitor (IC50=3.1 nM (PRMT1), 48 nM (PRMT3), 1148 nM (PRMT4), 5.7 nM (PRMT6), 1.7 nM (PRMT8)). GSK3368715 dihydrochloride (EPZ019997 dihydrochloride) produces a shift in arginine methylation states, alters exon usage, and has strong anti-cancer activity[1].

  • CAS Number: 1628925-77-8
  • MF: C20H40Cl2N4O2
  • MW: 439.46
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

danusertib

Danusertib is a pyrrolo-pyrazole and aurora kinase inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively.

  • CAS Number: 827318-97-8
  • MF: C26H30N6O3
  • MW: 474.555
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 664.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.5±31.5 °C

2,4-Pentadienoic acid,5-phenyl-,(2S,3aR,3bS,3cS,4aR,5S,5aS,8aR,8bR,9R,10R,10aS)-3a,3b,3c,4a,5,5a,8a,9,10,10a-decahydro-5,5a-dihydroxy-4a-(hydroxymethyl)-7,9-dimethyl-10a-(1-methylethenyl)-6-oxo-2-phen

Mezerein is a PKC activator that exhibits antileukemic properties. Mezerein inhibits the growth of yeast expressing PKC alpha (IC50=1190 nM), PKC beta1 (IC50=908 nM), and PKC delta (IC50=141 nM) but not of yeast expressing PKC[1][2].

  • CAS Number: 34807-41-5
  • MF: C38H38O10
  • MW: 654.70200
  • Catalog: PKC
  • Density: 1.43 g/cm3
  • Boiling Point: N/A
  • Melting Point: 258-262ºC
  • Flash Point: N/A

Bisindolylmaleimide IV

Bisindolylmaleimide IV (Arcyriarubin A) is a potent protein kinase C (PKC) inhibitor, with IC50s ranging from 0.1 to 0.55 μM. Bisindolylmaleimide IV also inhibits PKA (IC50=3.1-11.8μM)[1]. Bisindolylmaleimide IV is a potent, selective inhibitor of human cytomegalovirus (HCMV) replication in cell culture with an IC50 of 0.2 μM[2].

  • CAS Number: 119139-23-0
  • MF: C20H13N3O2
  • MW: 327.336
  • Catalog: CMV
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 690.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.2±31.5 °C

OUL245

OUL245 is a 7-Hydroxy derivative, and a selectively PARP2 inhibitor (IC50=44 nM). OUL245 also inhibits other PARP and TNKS enzymes with IC50s of 2.9-8.8 μM[1].

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

Daminozide

Daminozide(DMASA; DIMG; B 995), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily.IC50 Value: Target: KDM2/7 JmjCInhibition of shoot elongation in dwarf and tall peas by the 1,1-dimethylhydrazide of succinic acid (B-995) was correlated with the inhibition of the oxidation of tryptamine-2-C(14) to indoleacetaldehyde-2-C(14) in homogenates prepared from epicotyls of young plants treated with B-995. The growth-retarding action of B-995 is attributed to the formation of 1,1-dimethylhydrazine in vivo. This hydrazine strongly inhibited tryptamine oxidation by pea epicotyl homogenates[1]. Daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily[2].in vitro: Essential oil content increased with increasing levels of gibberellins and decreased when gibberellin biosynthesis was blocked withdaminozide. With increasing levels of gibberellins, 1,8-cineole and camphor contents increased. Daminozide blocked the accumulation of alpha- and beta-thujone.[3].in vivo:

  • CAS Number: 1596-84-5
  • MF: C6H12N2O3
  • MW: 160.171
  • Catalog: Histone Demethylase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 329.5±44.0 °C at 760 mmHg
  • Melting Point: 162-164 °C(lit.)
  • Flash Point: 153.1±28.4 °C

UMB-32

A novel a potent, selective inhibitor of BRD4 with Kd of 550 nM, cellular IC50 of 724 nM; also potently binds to the TAF1 (560 nM) and TAF1L (1.3 uM) bromodomains; significantly induces HIV-1 reactivation.

  • CAS Number: 1635437-39-6
  • MF: C21H23N5O
  • MW: 361.440
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ilorasertib hydrochloride

Ilorasertib hydrochloride (ABT-348 hydrochloride) is a potent and ATP-competitive multitargeted kinase inhibitor, which inhibits Aurora C, Aurora B, and Aurora A with IC50s of 1 nM, 7 nM, 120 nM, respectively. Ilorasertib hydrochloride (ABT-348 hydrochloride) also suppresses RET tyrosine kinase, PDGFRβ and Flt1 with IC50s of 7 nM, 3 nM and 32 nM, respectively[1].

  • CAS Number: 1847485-91-9
  • MF: C25H22ClFN6O2S
  • MW: 525.00
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT3-IN-18

STAT3-IN-18 (compound SPP) is a platinum (IV) complex with an axial ligand derived from sandalwood. STAT3-IN-18 inhibits the JAK2-STAT3 pathway in breast cancer (BC) cells, with anti-proliferative activity. STAT3-IN-18 activates caspase-3 and increases cleaved polyADP-ribose polymerase to induce apoptosis. STAT3-IN-18 promotes maturation and antigen presentation of dendritic cells and demonstrates safety in vivo.

  • CAS Number: 2668267-41-0
  • MF: C18H24Cl2N2O6Pt
  • MW: 630.38
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC2399

UNC2399, a biotinylated UNC1999, is a selective EZH2 degrader, maintaining high in vitro potency for EZH2, with an IC50 of 17 nM[1][2].

  • CAS Number: 2412791-72-9
  • MF: C48H66N10O7S
  • MW: 927.17
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC3/6-IN-2

HDAC3/6-IN-2 (compound 15) is a potent HDAC6 and HDAC3 inhibitor, with IC50 values of 0.368 and 0.635 μM, respectively. HDAC3/6-IN-2 shows antitumor activity, and induces cancer cell apoptosis. HDAC3/6-IN-2 decreases the levels of HDAC6 and HDAC3, associated with upregulation of acetylated H3 and α-tubulin[1].

  • CAS Number: 2417510-17-7
  • MF: C49H67N5O6
  • MW: 822.09
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salermide

Salermide is an inhibitor of Sirt1 and Sirt2; can cause strong cancer-specific apoptotic cell death.

  • CAS Number: 1105698-15-4
  • MF: C26H22N2O2
  • MW: 394.465
  • Catalog: Sirtuin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 666.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 357.0±30.1 °C

Ilunocitinib

Ilunocitinib (compound 27) is a JAK inhibitor (extracted from patent WO2009114512A1)[1].

  • CAS Number: 1187594-14-4
  • MF: C17H17N7O2S
  • MW: 383.43
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Talazoparib

Talazoparib (BMN-673) is a highly potent PARP1/2 inhibitor with Kis of 1.2 nM and 0.87 nM, respectively.

  • CAS Number: 1207456-01-6
  • MF: C19H14F2N6O
  • MW: 380.351
  • Catalog: PARP
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EPZ015666

EPZ015666 is an orally available inhibitor of PRMT5 with an IC50 of 22 nM.

  • CAS Number: 1616391-65-1
  • MF: C20H25N5O3
  • MW: 383.444
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 686.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.9±31.5 °C

PKCiota-IN-2

PKCiota-IN-2 is a potent PKCiota (PKC-ι) inhibitor with an IC50 of 2.8 nM. PKCiota-IN-2 also inhibits PKC-α and PKC-ε with IC50s of 71 nM and 350 nM, respectively[1].

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

Sirtuin modulator 5

Sirtuin modulator 5 is a sirtuin modulating agent. Sirtuin modulator 5 can activate SIRT1 with a DC50 value of <50 μM. Sirtuin modulator 5 can be used for increasing the lifespan of a cell and used for the research of variety of diseases including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity[1].

  • CAS Number: 694469-31-3
  • MF: C24H23N3O4
  • MW: 417.45712
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pamiparib

Pamiparib is a PARP inhibitor which can be used for the treatment of various cancers including the solid tumor, extracted from patent WO 2013097225 A1.

  • CAS Number: 1446261-44-4
  • MF: C16H15FN4O
  • MW: 298.315
  • Catalog: PARP
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CYT387

Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively. CYT387 shows much less activity against JAK3.

  • CAS Number: 1056634-68-4
  • MF: C23H22N6O2
  • MW: 414.460
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MC 1742

MC1742 is a potent HDAC inhibitor, with IC50s of 0.1 μM, 0.11 μM, 0.02 μM, 0.007 μM, 0.61 μM, 0.04 μM and 0.1 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, HDAC10 and HDAC11, respectively. MC1742 can increase acetyl-H3 and acetyl-tubulin levels and inhibits cancer stem cells growth. MC1742 can induce growth arrest, apoptosis, and differentiation in sarcoma CSC[1].

  • CAS Number: 1776116-74-5
  • MF: C21H21N3O3S
  • MW: 395.47
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRM/BRG1 ATP Inhibitor-4

BRM/BRG1 ATP Inhibitor-4 is a BRG1/BRM inhibitor. BRM/BRG1 ATP Inhibitor-4 can be used for the research of cancers and BAF complex-related disorders[1].

  • CAS Number: 2422030-94-0
  • MF: C25H32N6O3S
  • MW: 496.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KB02-JQ1

KB02-JQ1 is a highly selective and PROTAC-based BRD4 degrader (molecular glue), but does not degrade BRD2 or BRD3. KB02-JQ1 promotes BRD4 degradation by covalently modifying DCAF16 (E3 ligase) and can improve the durability of protein degradation in biological systems. JQ1 binds ubiquitin E3 ligase ligand KB02 via a linker to form KB02-JQ1[1].

  • CAS Number: 2384184-44-3
  • MF: C38H43Cl2N7O6S
  • MW: 796.76
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP/p300-IN-17

CBP/p300-IN-17 (compound 7) is a potent EP300/CBP HAT inhibitor with IC50s of 0.18, 0.69 µM for HAT EP300 and LK2 H3K27, respectively[1].

  • CAS Number: 2259640-87-2
  • MF: C25H28N4O3
  • MW: 432.51
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amarogentin

Amarogentin is a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots. Amarogentin exhibits many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. Amarogentin exerts hepatoprotective and immunomodulatory effects. Amarogentin promotes apoptosis, arrests G2/M cell cycle and downregulates of PI3K/Akt/mTOR signalling pathways. Amarogentin exerts beneficial vasculo-metabolic effect by activating AMPK[1][2][3].

  • CAS Number: 21018-84-8
  • MF: C29H30O13
  • MW: 586.541
  • Catalog: Apoptosis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 928.5±65.0 °C at 760 mmHg
  • Melting Point: 229-230ºC
  • Flash Point: 306.9±27.8 °C