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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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(+)-JQ1

(+)-JQ-1 is a BET bromodomain inhibitor, with IC50s of 77 and 33 nM for the first and second bromodomain (BRD4(1/2)).

  • CAS Number: 1268524-70-4
  • MF: C23H25ClN4O2S
  • MW: 456.988
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 610.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 322.9±34.3 °C

BET-IN-15

BET-IN-15 (compound 1) is a potent and orally active BET inhibitor with IC50 values of 0.64, 0.25 nM for BRD4-BD1, BRD4-BD2, respectively. BET-IN-15 shows antiproliferative activity[1].

  • CAS Number: 2408994-22-7
  • MF: C21H18F2N4O3S
  • MW: 444.45
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Resveratrol analog 2

Resveratrol analog 2 is an analog of Resveratrol (HY-16561). Resveratrol is a natural polyphenolic phytoalexin that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties[1].

  • CAS Number: 915378-82-4
  • MF: C16H13FO3
  • MW: 272.27
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TH1834 dihydrochloride

TH1834 dihydrochloride (TH-1834, TH 1834) is a novel potent specific histone acetyltransferase Tip60 inhibitor; induces apoptosis in breast cancer cell lines with more cytotoxicity than staurosporine; increases the γH2AX foci in the cancer cell lines PC-3 and DU-145 combined with IR; induces apoptosis and increases unrepaired DNA damage in breast cancer cells.

  • CAS Number: 2108830-09-5
  • MF: C33H42Cl2N6O3
  • MW: 641.638
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nesuparib

Nesuparib is a potent inhibitor of PARP. Nesuparib is useful for the research of neuropathic pain, neurodegenerative disease, and cardiovascular disease (extracted from patent WO2016200101A2)[1].

  • CAS Number: 2055357-64-5
  • MF: C23H24N6O
  • MW: 400.48
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Beta-Amyloid(1-40)

β-Amyloid (1-40) is a primary protein in plaques found in the brains of patients with Alzheimer's disease.

  • CAS Number: 131438-79-4
  • MF: C194H295N53O58S
  • MW: 4329.867
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK 5959

GSK-5959 is a potent, selective and cell permeable BRPF1 bromodomain inhibitor with IC50 ~ 80 nM. Exhibits >100-fold selectivity for BRPF1 over a panel of 35 other bromodomains, including BRPF2/3 and BET family bromodomains.IC50 value: 80 nMTarget: BRPF1in vitro: GSK-5959 inhibits BRPF1 interaction with histone H3. A cellular protein interaction assay measuring the displacement of NanoLuc-tagged BRPF1 bromodomain from Halotagged histone H3 is employed to demonstrate GSK-5959 is cell permeability and disruption of chromatin binding with IC50 of 0.98 μM. GSK-5959 is used at 10 μM final concentration in various in vitro assays.

  • CAS Number: 901245-65-6
  • MF: C22H26N4O3
  • MW: 394.467
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 527.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.7±30.1 °C

depudecin

Depudecin ((-)-Depudecin) is a histone deacetylase (HDAC) inhibitor. Depudecin can be isolated from the fungus Alternaria brassicicola[1][2].

  • CAS Number: 139508-73-9
  • MF: C11H16O4
  • MW: 212.24200
  • Catalog: HDAC
  • Density: 1.415g/cm3
  • Boiling Point: 369.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 177.2ºC

MOZ-IN-2

MOZ-IN-2 is an inhibitor of protein MOZ, a member of histone acetyltransferases, with an IC50 of 125 μM.

  • CAS Number: 2055397-88-9
  • MF: C17H13FN4O3S
  • MW: 372.3735232
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YLF-466D

YLF-466D is a newly developed AMPK activator, which inhibits platelet aggregation.

  • CAS Number: 1273323-67-3
  • MF: C29H20ClNO3
  • MW: 465.92700
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZT55

ZT55 (JAK inhibitor ZT55) is a novel potent, highly-selective tyrosine kinase JAK2 inhibitor with IC50 of 31 nM; displays no significant activity against JAK1/3 (IC50>10 uM); exhibits potent effects on the cellular JAK-STAT pathway, inhibiting tyrosine phosphorylation in JAK2V617F and downstream STAT3/5 transcription factors; inhibits the proliferation of the JAK2V617F-expressing HEL cell line, leading to cell cycle arrest at the G2/M phase and induction of caspase-dependent apoptosis; significantly suppressed the growth of HEL xenograft tumors in vivo, blocks erythroid colony formation of peripheral blood hematopoietic progenitors from patients carrying the JAK2V617F mutation.

  • CAS Number: 2138488-38-5
  • MF: C17H16N2O3
  • MW: 296.326
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-AMINO-1,8-NAPHTHALIMIDE

4-Aminonaphthalimide is a potent PARP inhibitor and potentiates the cytotoxicity of γ-radiation in cancer cells[1].

  • CAS Number: 1742-95-6
  • MF: C12H8N2O2
  • MW: 212.20
  • Catalog: PARP
  • Density: 1.105 g/mL at 25ºC(lit.)
  • Boiling Point: 544.1ºC at 760 mmHg
  • Melting Point: 360ºC
  • Flash Point: 282.8ºC

Tankyrase-IN-3

Tankyrase-IN-3 is a tankyrase 1 (TNKS1) inhibitor with an IC50 value of 22 nM. Tankyrase-IN-3 can be used for the research of cancer[1].

  • CAS Number: 938893-79-9
  • MF: C21H21N5O4
  • MW: 407.42
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WDR5 0103

WDR5-0103 is a potent and selective WD repeat-containing protein 5 (WDR5) antagonist with Kd of 450 nM.IC50 value: 450 nM (Kd)Target: WDR5in vitro: WDR5-0103 inhibits MLL catalytic activity with an IC50 value of 39±10 μM. An increase in MLL complex concentration resulted in proportional increase in IC50 values for WDR5-0103 (83±10 and 280±12 μM at concentrations of 500 and 1000 nM of the core trimeric MLL complex respectively). These data are consistent with a mechanism of action in which WDR5-0103 antagonizes the interaction of WDR5 with MLL by competing with MLL for their mutual binding site on WDR5.

  • CAS Number: 890190-22-4
  • MF: C21H25N3O4
  • MW: 383.441
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 495.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 253.3±28.7 °C

2'-Deoxy-5-fluorcytidine

5-Fluoro-2'-deoxycytidine, a fluoropyrimidine nucleoside analogue, is a DNA methyltransferase (DNMT) inhibitor. 5-Fluoro-2'-deoxycytidine is a tumor-selective prodrug of the potent thymidylate synthase inhibitor 5-fluoro-2′-dUMP[1][2].

  • CAS Number: 10356-76-0
  • MF: C9H12FN3O4
  • MW: 245.208
  • Catalog: DNA Methyltransferase
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 465.0±55.0 °C at 760 mmHg
  • Melting Point: 196 °C
  • Flash Point: 235.0±31.5 °C

A1874

A1874 is a nutlin-based and BRD4-degrading PROTAC with a DC50 of 32 nM (induce BRD4 degradation in cells). Effective in inhibiting many cancer cell lines proliferation[1].

  • CAS Number: 2064292-12-0
  • MF: C58H62Cl3F2N9O7S
  • MW: 1173.59
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS 21311

TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC50 of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC50s of 13, 68, and 3 nM, respectively[1].

  • CAS Number: 1260181-14-3
  • MF: C27H25F3N4O4
  • MW: 526.50700
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPI-1612

P300/CBP-IN-6 is a p300/CBP histone acetyltransferase (HAT) inhibitor extracted from patent WO2019161162A1, compound 33, has an IC50 of 330 nM for p300 HAT[1].

  • CAS Number: 2374971-81-8
  • MF: C27H26N6O
  • MW: 450.53
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

script

Nullscript is a negative control for Scriptaid. Nullscript is a known inactive analog of Scriptaid[1]. Scriptaid is a representative HDAC inhibitor[2]. Nullscript inhibits Cryptosporidium (C. parvum) growth with the IC50 value of 2.1 μM[3].

  • CAS Number: 300816-11-9
  • MF: C16H14N2O4
  • MW: 298.293
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TH1834

TH1834 (TH-1834, TH 1834) is a novel potent specific histone acetyltransferase Tip60 inhibitor; induces apoptosis in breast cancer cell lines with more cytotoxicity than staurosporine; increases the γH2AX foci in the cancer cell lines PC-3 and DU-145 combined with IR; induces apoptosis and increases unrepaired DNA damage in breast cancer cells.

  • CAS Number: 2108830-08-4
  • MF: C33H40N6O3
  • MW: 568.722
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tenovin-6

Tenovin-6 is a water soluble inhibitor of SIRT1 and SIRT2, slightly inhibits HDAC8, and is also a potent activator of p53, with IC50s of 21 μM, 10 μM, and 67 μM for SirT1, SirT2, and SirT3, respectively.

  • CAS Number: 1011557-82-6
  • MF: C25H34N4O2S
  • MW: 454.628
  • Catalog: MDM-2/p53
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Amodiaquine

Amodiaquine (Amodiaquin), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor. Amodiaquine is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC50 of ~20 μM. Anti-inflammatory effect[1][2][3][4].

  • CAS Number: 86-42-0
  • MF: C20H22ClN3O
  • MW: 355.861
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 478.0±45.0 °C at 760 mmHg
  • Melting Point: 208°C
  • Flash Point: 242.9±28.7 °C

JPS036

JPS036 is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). JPS036 degrades class I histone deacetylase (HDAC). JPS036 is potent HDAC1/2 degrader correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells[1].

  • CAS Number: 2669785-85-5
  • MF: C51H66FN7O7S
  • MW: 940.18
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nicotinamide riboside chloride

Nicotinamide riboside chloride is a crystal form of Nicotinamide riboside (NR) chloride which is a nicotinamide adenine dinucleotide (NAD[+]) precursor vitamin. Nicotinamide riboside chloride increases NAD[+] levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside chloride is used in dietary supplements[1].

  • CAS Number: 23111-00-4
  • MF: C11H15ClN2O5
  • MW: 290.70000
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ENMD-2076

ENMD-2076 is a multi-targeted kinase inhibitor with IC50s of 1.86, 14, 58.2, 15.9, 92.7, 70.8, 56.4 nM for Aurora A, Flt3, KDR/VEGFR2, Flt4/VEGFR3, FGFR1, FGFR2, Src, PDGFRα, respectively.

  • CAS Number: 934353-76-1
  • MF: C21H25N7
  • MW: 375.470
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 535.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 277.4±30.1 °C

OG-L002

OG-L002 is a potent and highly selective LSD1 inhibitor with an IC50 of 0.02 μM. OG-L002 is a potent monoamine oxidases (MAO) inhibitor with IC50s of 1.38 μM and 0.72 μM for MAO-A and MAO-B, respectively. OG-L002 potently inhibits the expression of HSV IEgenes[1].

  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 416.7±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 205.8±28.7 °C

BN-104

Menin-MLL inhibitor 27 can inhibit the Menin-MLL interaction and can be used in cancer research, such as acute myeloid leukemia[1].

  • CAS Number: 2938995-50-5
  • MF: C31H35FN8O2
  • MW: 570.66
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP10-IN-3

PARP10-IN-3 is a selective mono‐ADP‐ribosyltransferase PARP10 inhibitor with an IC50 of 480 nM for human PARP10. PARP10-IN-3 reveals potent inhibition on PARP2 and PARP15 with IC50s of 1.7 μM for human PARP2 and human PARP15, respectively[1].

  • CAS Number: 2225800-19-9
  • MF: C14H12N2O3
  • MW: 256.26
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET bromodomain inhibitor 1

BET bromodomain inhibitor 1 is an orally active, selective bromodomain and extra-terminal (BET) bromodomain inhibitor with an IC50 of 2.6 nM for BRD4. BET bromodomain inhibitor 1 binds to BRD2(2), BRD3(2), BRD4(1), BRD4(2), and BRDT(2) with high affinities (Kd values of 1.3 nM, 1.0 nM, 3.0 nM, 1.6 nM, 2.1 nM, respectively). bromodomain inhibitor 1 has anti-cancer activity[1].

  • CAS Number: 2411226-02-1
  • MF: C22H19F2N3O4S
  • MW: 459.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06263276

PF-06263276 (PF 6263276) is a potent and selective pan-JAK inhibitor, with IC50s of 2.2 nM, 23.1 nM, 59.9 nM and 29.7 nM for JAK1, JAK2, JAK3 and TYK2, respectively[1].

  • CAS Number: 1421502-62-6
  • MF: C31H31FN8O2
  • MW: 566.638
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A