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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Apoptosis >
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GNE-886

GNE-886 is a potent and selective CECR2 bromodomain inhibitor with IC50 of 16 nM; shows a wide selectivity over the 40 bromodomains, >100-fold selectivity over BRD9, BRD7, TAF1(2), and BRD4(1); has a highly favorable measured kinetic solubility of 122 uM and is an appropriate in vitro tool compound for the CECR2 bromodomain.

  • CAS Number: 2101957-05-3
  • MF: C28H30N6O3
  • MW: 498.576
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 796.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 435.4±32.9 °C

PYRIDINE-2-CARBOXAMIDE

Picolinamide (2-Picolinamide) is an inhibitor of Poly(ADP-ribose) synthetase of nuclei from rat pancreatic islet cells[1][3].

  • CAS Number: 1452-77-3
  • MF: C6H6N2O
  • MW: 122.125
  • Catalog: PARP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 257.7±32.0 °C at 760 mmHg
  • Melting Point: 110 °C (dec.)(lit.)
  • Flash Point: 109.7±25.1 °C

KDM5B-IN-3

KDM5B-IN-3 (Compound 5) is a histone lysine specific demethylase 5B (KDM5B/JARID1B) inhibitor with an IC50 of 9.32 μM. KDM5B-IN-3 can be used for the research of gastric cancer[1].

  • CAS Number: 1385101-10-9
  • MF: C19H25ClN4O2
  • MW: 376.88
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Quisinostat

Quisinostat (JNJ-26481585) is an orally available, potent HDAC inhibitor with an IC50 of 0.11 nM for HDAC1.

  • CAS Number: 875320-29-9
  • MF: C21H26N6O2
  • MW: 394.47000
  • Catalog: HDAC
  • Density: 1.358g/cm3
  • Boiling Point: 615.103ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 325.803ºC

Bisindolylmaleimide X HCl

Bisindolylmaleimide X hydrochloride (BIM-X hydrochloride) is a potent protein kinase C (PKC) inhibitor[1].

  • CAS Number: 145317-11-9
  • MF: C26H25ClN4O2
  • MW: 460.955
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Olinone

Olinone is a selective BRD4 BrD1 inhibitor[1]. Olinone accelerates the progression of mouse primary oligodendrocyte progenitors toward differentiation[2].

  • CAS Number: 1770789-37-1
  • MF: C17H21N3O2
  • MW: 299.37
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 675.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.4±31.5 °C

Momelotinib-d10

Momelotinib-d10 (CYT387-d10) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally active and ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively, shows much less activity against JAK3[1][2].

  • CAS Number: 1619927-69-3
  • MF: C23H12D10N6O2
  • MW: 424.52
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-901-d3

TAK-901-d3 is the deuterium labeled TAK-901. TAK-901 is a multi-targeted aurora inhibitor with IC50s of 21 and 15 nM for aurora A and B, respectively[1][2].

  • CAS Number: 1346603-28-8
  • MF: C28H29D3N4O3S
  • MW: 507.66
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OUL232

OUL232 is a potent inhibitor of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15. OUL232 is the most potent PARP10 inhibitor described to date (IC50=7.8 nM), as well as the first PARP12 inhibitor ever reported[1].

  • CAS Number: 943119-42-4
  • MF: C10H10N4O2S
  • MW: 250.28
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mitoxantrone-d8

Mitoxantrone-d8 (mitozantrone-d8) is the deuterium labeled Mitoxantrone. Mitoxantrone is a topoisomerase II inhibitor and also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM[1][2].

  • CAS Number: 1189974-82-0
  • MF: C22H20D8N4O6
  • MW: 452.53000
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 145 °C
  • Flash Point: N/A

JAK-IN-14

JAK-IN-14 is a potent and selective JAK1 inhibitor, with an IC50 of <5 μM. JAK-IN-14 is >8-fold more selective for JAK1 than JAK2 and JAK3 (Patent WO2016119700A1, compound 16)[1].

  • CAS Number: 1973485-06-1
  • MF: C19H15FN4O
  • MW: 334.35
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromodomain inhibitor-9

Bromodomain inhibitor-9 is a Bromodomains inhibitor that selectively inhibits BRD4-1 (Kd: 12 nM). Bromodomain inhibitor-9 can be used in the research of diseases or conditions associated with systemic or tissue inflammation, lipid metabolism, fibrosis or chronic autoimmune diseases[1].

  • CAS Number: 1870849-34-5
  • MF: C24H28N4O5S
  • MW: 484.57
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Purinostat mesylate

Purinostat mesylate is a selective inhibitor of HDAC. Purinostat mesylate inhibits class I and class IIb HDACs with IC50s from 0.81 to 11.5 nM. Purinostat mesylate induces apoptosis and affects cell cycle of LAMA84 and 188 BL-2 cells, and shows potently anti-leukemia effects in vivo. Purinostat mesylate can be used for the research of lymphoblastic leukemia[1].

  • CAS Number: 2650188-32-0
  • MF: C24H30N10O6S
  • MW: 586.62
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SD-1029

SD-1029 (NSC 371488) is a potent inhibitor of Stat3 activation, suppresses EGFP-Stat3 nuclear translocation at 10 uM in both BHK-21 and U2-OS cells; inhibits Stat3-mediated antiapoptotic protein expression (Bcl-XL, MCL-1, and survivin), and suppresses phosphotyrosine levels of JAK2; inhibits IL-6 or oncostatin-induced Stat3 nuclear translocation at micromolar range, enhances apoptosis induced by paclitaxel in human cancer cells.

  • CAS Number: 118372-34-2
  • MF: C25H30Cl2N2O32HBr
  • MW: 639.247
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MLN8054

MLN8054 is a potent, selective and orally available aurora A kinase inhibitor with an IC50 of 4 nM.

  • CAS Number: 869363-13-3
  • MF: C25H15ClF2N4O2
  • MW: 476.86
  • Catalog: Aurora Kinase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 429.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 213.5±28.7 °C

GSK-3484862

GSK-3484862 is a non-covalent inhibitor for Dnmt1. GSK-3484862 induces DNA hypomethylation to against cancer[1].

  • CAS Number: 2170136-65-7
  • MF: C19H19N5OS
  • MW: 365.45
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACY-1083

ACY-1083 is a selective and brain-penetrating HDAC6 inhibitor with an IC50 of 3 nM and is 260-fold more selective for HDAC6 than all other classes of HDAC isoforms. ACY-1083 effectively reverses chemotherapy-induced peripheral neuropathy[1].

  • CAS Number: 1708113-43-2
  • MF: C17H18F2N4O2
  • MW: 348.35
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YUKA1

YUKA1 is a potent and cell permeable Lysine demethylase 5A (KDM5A) inhibitor, with an IC50 of 2.66 μM, less active on KDM5C (IC50, 7.12 μM), and is inactive on KDM5B, KDM6A or KDM6B. YUKA1 increases H3K4me3 levels in human cells with anti-cancer activity[1].

  • CAS Number: 708991-09-7
  • MF: C13H16N4O2S
  • MW: 292.36
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Metformin HCl

Metformin (hydrochloride) is an FDA approved first-line drug for the treatment of type 2 diabetes. Metformin decreases hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory-chain complex 1.

  • CAS Number: 1115-70-4
  • MF: C4H12ClN5
  • MW: 165.625
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 224.1ºC at 760 mmHg
  • Melting Point: 223-226 °C(lit.)
  • Flash Point: 89.3ºC

Myristoyl-Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu-OH

N-myristoyl-RKRTLRRL inhibits binding of PKC substrates. N-myristoyl-RKRTLRRL inhibits Ca2+- and phosphatidylserine (PS)-dependent histone phosphorylation with IC50 of 5 μM.? histone phosphorylation with IC50 of 80 μM[1][2].

  • CAS Number: 152246-40-7
  • MF: C60H117N21O11
  • MW: 1308.71000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD4 Degrader-5

PROTAC BRD4 Degrader-5 is a PROTAC-based BRD4 degrader. PROTAC BRD4 Degrader-5 can potent degrade BRD4 in HER2 positive and negative breast cancer cell lines[1].

  • CAS Number: 2409538-70-9
  • MF: C50H62ClN9O8S2
  • MW: 1016.67
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R 59-022 hydrochloride

R 59-022 (DKGI-I) hydrochloride is a DGK inhibitor (IC50: 2.8 µM). R 59-022 hydrochloride inhibits the phosphorylation of OAG to OAPA. R 59-022 hydrochloride is a 5-HT Receptor antagonist, and activates protein kinase C (PKC). R 59-022 hydrochloride potentiates thrombin-induced diacylglycerol production in platelets and inhibits phosphatidic acid production in neutrophils[1][2][3][4].

  • CAS Number: 93076-98-3
  • MF: C27H27ClFN3OS
  • MW: 496.04
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hu7691

Hu7691 is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2360523-76-6
  • MF: C22H22ClF3N4O
  • MW: 450.88
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MI-503

MI-503 is a highly potent and orally bioavailable small molecule inhibitor of the menin-mLL interaction.

  • CAS Number: 1857417-13-0
  • MF: C28H27F3N8S
  • MW: 564.628
  • Catalog: Histone Methyltransferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 782.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 427.3±32.9 °C

JAK3/BTK-IN-5

JAK3/BTK-IN-5 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-5 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147953A1, compound 35)[1]

  • CAS Number: 2673196-75-1
  • MF: C19H22ClN7O2
  • MW: 415.88
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Psammaplin A

Psammaplin A, a marine metabolite, is a potent inhibitor of HDAC and DNA methyltransferases. Psammaplin A ia a highly potent and selective DAC1 inhibitor with an IC50 of 0.9 nM. Psammaplin A possess the antimicrobial effect on the Gram-positive bacteria and inhibits DNA synthesis and DNA gyrase activity. Antitumor Activity[1][2].

  • CAS Number: 110659-91-1
  • MF: C22H24Br2N4O6S2
  • MW: 664.38700
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

25-Deacetylcucurbitacin A

25-Deacetylcucurbitacin A is a Cucurbitane-Type triterpenoid and has the potential to be an anti-cancer agent and JAK/STAT3 signaling pathway inhibitor[1].

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

PKC-theta inhibitor

PKC-theta inhibitor is a selective PKC-θinhibitor, with an IC50 of 12 nM.

  • CAS Number: 736048-65-0
  • MF: C20H25F3N6O3
  • MW: 454.45
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BRD4 Degrader-6

PROTAC BRD4 Degrader-6 (compound 32a) is a potent small-molecule BRD4 degrader with IC50 value of 2.7 nM for BRD4 BD1. PROTAC BRD4 Degrader-6 potently degrades BRD4 protein and inhibits the expression of c-Myc. PROTAC BRD4 Degrader-6 inhibits the proliferation of pancreatic cancer cell line BxPC3 and induces apoptosis. PROTAC BRD4 Degrader-6 can be used for human pancreatic cancer research[1].

  • CAS Number: 2410947-56-5
  • MF: C43H40F2N10O10S
  • MW: 926.90
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-7

Tyk2-IN-7 (Compound 48) is a TYK2 JH2 inhibitor, binds to TYK2 JH2 domain with IC50 and Ki.app of 0.00053 μM and 0.00007 μM, respectively. Tyk2-IN-7 (Compound 48) provides a highly selective alternative to conventional TYK2 orthosteric inhibitors, inhibits TYK2/JAK1/JAK2 kinase domain. Tyk2-IN-7 (Compound 48) provides robust inhibition in a mouse IL-12-induced IFNγ pharmacodynamic model as well as efficacy in an IL-23 and IL-12-dependent mouse colitis model[1].

  • CAS Number: 1609391-90-3
  • MF: C18H15D3N6O3S
  • MW: 401.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A