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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BY27

BY27 is a potent and selective BET BD2 inhibitor, shows 38, 5, 7, and 21-fold BD1/BD2 selectivity for BRD2, BRD3, BRD4, and BRDT. Anti-cancer activity[1].

  • CAS Number: 2247236-59-3
  • MF: C22H21ClN6
  • MW: 404.90
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

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

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

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

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

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

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

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

Protein Kinase C (530-558)

Protein Kinase C (530-558), a peptide fragment of protein kinase C (PKC), is a potent PKC activator. Protein Kinase C (530-558) significantly inhibits osteoclastic bone resorption[1].

  • CAS Number: 122613-29-0
  • MF: C148H221N35O50S2
  • MW: 3354.67000
  • Catalog: PKC
  • Density: 1.4±0.1g/cm3
  • Boiling Point: 3001.7±65.0°C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1769.2±34.3°C

JAK-IN-15

JAK-IN-15 is a JAK inhibitor. WO2016119700A1 (Compound 15)[1].

  • CAS Number: 1973485-05-0
  • MF: C22H23FN4O3S
  • MW: 442.51
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Baricitinib

Baricitinib is a selective and orally bioavailable JAK1 and JAK2 inhibitor with IC50s of 5.9 nM and 5.7 nM, respectively.

  • CAS Number: 1187594-09-7
  • MF: C16H17N7O2S
  • MW: 371.417
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 707.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.5±35.7 °C

3β,6α,12β-Dammar-E-20(22)-ene-3,6,12,25-tetraol

3β,6α,12β-Dammar-E-20(22)-ene-3,6,12,25-tetraol, a SIRT1 activator, exhibits significant stimulation of SIRT1 activity. Anti-tumor activity[1].

  • CAS Number: 97744-95-1
  • MF: C30H52O4
  • MW: 476.732
  • Catalog: Sirtuin
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 589.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.1±24.7 °C

JAK2-IN-4

JAK2-IN-4 (compound 16h) is a selective JAK2/JAK3 inhibitor, with IC50 values of 0.7 nM and 23.2 nM for JAK2 and JAK3, respectively[1].

  • CAS Number: 1438284-00-4
  • MF: C23H27N5O4S
  • MW: 469.56
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cl-amidine

Cl-amidine is a peptidylarginine deminase (PAD) inhibitor, with an IC50 5.9 μM for PAD4.

  • CAS Number: 913723-61-2
  • MF: C14H19ClN4O2
  • MW: 310.78
  • Catalog: Inflammation/Immunology
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT-9283 L-lactate

AT9283 lactic acid is a multi-targeted kinase inhibitor with potent activity against Aurora A/B, JAK2/3, Abl (T315I) and Flt3 (IC50s ranging from 1 to 30 nM). AT9283 lactic acid inhibits growth and survival of multiple solid tumors in vitro and in vivo[1][2].

  • CAS Number: 896466-76-5
  • MF: C22H29N7O5
  • MW: 471.51
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARTD10/PARP10-IN-2

ARTD10/PARP10-IN-2 (compound 19) is a potent and non-selective PARP inhibitor, targeting to mono-ADP-ribosyltransferases ARTD10/PARP10 and poly(ADP-ribose) polymerase-1 ARTD1/PARP1 with IC50s of 2.0 μM, and 9.7 μM, respectively[1].

  • CAS Number: 1708103-69-8
  • MF: C12H13N3O3
  • MW: 247.25
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BETd-260

BETd-260 is a potent BET degrader based on PROTAC technology, with an IC50 of 30 pM against BRD4 protein in RS4;11 leukemia cell line.

  • CAS Number: 2093388-62-4
  • MF: C43H46N10O6
  • MW: 798.89
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EB 47, PARP-1 inhibitor

EB-47 dihydrochloride, 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: 1190332-25-2
  • MF: C24H29Cl2N9O6
  • MW: 610.450
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LSD1-IN-13

LSD1-IN-13 (compound 7e) is an orally active and potent LSD1 inhibitor, with an IC50 of 24.43 nM. LSD1-IN-13 can activate CD86 expression, with an EC50 of 470 nM. LSD1-IN-13 induces differentiation of AML (acute myeloid leukemia) cell lines[1].

  • CAS Number: 2170212-33-4
  • MF: C23H29N3O2S
  • MW: 411.56
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Inauhzin

Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer.

  • CAS Number: 309271-94-1
  • MF: C25H19N5OS2
  • MW: 469.581
  • Catalog: MDM-2/p53
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 773.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 421.7±35.7 °C

Bromodomain inhibitor-10

Bromodomain inhibitor-10 (compound 128) is a potent bromodomain inhibitor with Kds of 15.0, 2500 nM for BRD4-1 and BRD4-2, respectively. Bromodomain inhibitor-10 inhibits the production of IL12p40[1].

  • CAS Number: 1870849-58-3
  • MF: C20H20N4O3
  • MW: 364.40
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKCε (85-92)

PKCε (85-92) is a biological active peptide. (This peptide is the e-PKC specific activator, it also activates MARCKS phosphorylation in wild type cells, and has no effect on MARCKS phosphorylation in the cells derived from knockout mice.)

  • CAS Number: 207111-98-6
  • MF: C39H54N10O14
  • MW: 886.90
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OSU-2S

A non-immunosuppressive FTY720 analogue, PKCδ activator with higher antiproliferative potency with IC50 of 2.4, 2.4, and 3.5 uM in Huh7, Hep3B, and PLC5 cells, respectively; exhibited higher in vitro antiproliferative efficacy relative to FTY720 against HCC cells without cytotoxicity in normal hepatocytes, although devoid of S1P1 receptor activity; induces caspase-dependent apoptosis through ROS-dependent PKCδ activation in HCC tumor cells.

  • CAS Number: 1351056-65-9
  • MF: C21H37NO2
  • MW: 335.532
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A