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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PF-06821497

PF-06821497 (compound 23a) is a potent, selective and orally active Enhancer of Zeste Homolog 2 (EZH2) inhibitor, with a Ki value <0.1 nM against mutant Y641N EZH2. Exhibits robust tumor growth inhibition[1].

  • CAS Number: 1844849-10-0
  • MF: C22H24Cl2N2O5
  • MW: 467.34
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP-IN-1

CBP-IN-1 (compound 12) is a potent CBP inhibitor, with an IC50 of 1.5 nM. CBP-IN-1 also inhibits CBP BRET and BRD4(1), with IC50 values of 690 and 3100 nM, respectively[1].

  • CAS Number: 1936431-44-5
  • MF: C27H33F2N7O
  • MW: 509.59
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ505 (ditrifluoroacetate)

AZ505 ditrifluoroacetate is a potent and selective SMYD2 inhibitor with IC50 of 0.12 μM.

  • CAS Number: 1035227-44-1
  • MF: C33H40Cl2F6N4O8
  • MW: 805.59
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pocenbrodib

Pocenbrodib (compound II) is a CBP/p300 family of bromodomain inhibitor. Pocenbrodib has the potential for cancer research[1].

  • CAS Number: 2304372-79-8
  • MF: C28H32FN3O6
  • MW: 525.57
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ep300/CREBBP-IN-8

Ep300/CREBBP-IN-8 (Example 37) is a potent and orally active Ep300 and CREBBP inhibitor with IC50s of 0.014 and 0.018 μM, respectively. Ep300/CREBBP-IN-8 can be used for the research of cancer[1].

  • CAS Number: 2259641-24-0
  • MF: C25H27F2N5O3
  • MW: 483.51
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP7-IN-16

PARP7-IN-16 (compound 36) is a potent, selective and orally active inhibitor of PARP-1/2/7, with IC50s of 0.94, 0.87 and 0.21 nM, respectively. PARP7-IN-16 can be used for the research of breast cancer and prostate cancer[1].

  • CAS Number: 2435657-10-4
  • MF: C25H26FN4NaO4
  • MW: 488.49
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TUL01101

TUL01101 is a potent, selective and orally active JAK1 inhibitor, with an IC50s of 3, 37, 1517 and 36 nM for JAK1, JAK2, JAK3, and TYK2, respectively. TUL01101 can be used for the research of rheumatoid arthritis[1].

  • CAS Number: 2411222-97-2
  • MF: C22H25F2N5O2
  • MW: 429.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dihydro-5-azacytidine acetate

Dihydro-5-azacytidine acetate (DHAC), the nucleoside analog, is incorporated into DNA and inhibits DNA methylation. Dihydro-5-azacytidine acetate has an antitumor activity[1][2].

  • CAS Number: 2470972-18-8
  • MF: C10H18N4O7
  • MW: 306.27
  • Catalog: Nucleoside Antimetabolite/Analog
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ARV-825

ARV-825 is a BRD4 Inhibitor based on PROTAC technology. ARV-825 binds to BD1 and BD2 of BRD4 with Kds of 90 and 28 nM, respectively.

  • CAS Number: 1818885-28-7
  • MF: C46H47ClN8O9S
  • MW: 923.432
  • Catalog: Epigenetic Reader Domain
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNMT-IN-3

DNMT-IN-3 is an DNA Methyltransferase (DNMT) inhibitor, and plays an antimalarial role with IC50 of 60 nM against Plasmodium falciparum (Plasmodium). DNMT-IN-3 can be used for malaria related research[1].

  • CAS Number: 1683516-27-9
  • MF: C37H39N7O
  • MW: 597.75
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Seclidemstat

Seclidemstat (SP-2577) is a potent LSD1 inhibitor, with a mean IC50 of 127 nM.

  • CAS Number: 1423715-37-0
  • MF: C20H23ClN4O4S
  • MW: 450.939
  • Catalog: Histone Demethylase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Abrocitinib

Abrocitinib (PF-04965842) is a potent, oral active and selective JAK1 inhibitor, with IC50s of 29 and 803 nM for JAK1 and JAK2, respectively. Abrocitinib (PF-04965842) exhibits less active effect on TYK2 (IC50, 1.253 μM), and inhibits phosphorylation of STAT1,STAT3 and STAT5 after stimulation. Effective in autoimmune disease[1].

  • CAS Number: 1622902-68-4
  • MF: C14H21N5O2S
  • MW: 323.415
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H7

PKC-IN-5 (compound H-7) is a potent PKC (protein kinase C) inhibitor. At 100 μM, PKC-IN-5 completely inhibits both TPA (skin tumour promoter, 12-O-tetradecanoylphorbol-13-acetate) and phospholipase C-induced ODC (ornithine decarboxylase)[1].

  • CAS Number: 108930-17-2
  • MF: C14H19Cl2N3O2S
  • MW: 364.291
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: 495.3ºC at 760mmHg
  • Melting Point: 215-225 °C
  • Flash Point: 253.3ºC

AMPK activator 991

AMPK activator 991 is an allosteric AMPK activator, activates non-phosphorylated Thr172 AMPK in vitro binds to α1β1γ1 and α2β1γ1 with Kd of 0.13 and 0.17 uM, respectively.

  • CAS Number: 1219739-95-3
  • MF: C24H18ClN3O3
  • MW: 431.876
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-13

PRMT5-IN-13 is a selective inhibitor of protein arginine methyltransferase 5 (prmt5).

  • CAS Number: 2376795-15-0
  • MF: C18H17ClN4O4
  • MW: 388.80
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK343

GSK343 is a highly potent and selective EZH2 inhibitor with an IC50 of 4 nM.

  • CAS Number: 1346704-33-3
  • MF: C31H39N7O2
  • MW: 541.687
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 797.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 436.0±32.9 °C

JAK-IN-28

JAK-IN-28 (Compound 111) is a JAK inhibitor. JAK-IN-28 can be used for research of cancer or inflammatory diseases[1].

  • CAS Number: 2445500-22-9
  • MF: C20H18ClN7O
  • MW: 407.86
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DC_C66

DC_C66 is a cell-permeable, selective coactivator associated arginine methyltransferase 1 (CARM1) inhibitor with an IC50 of 1.8 μM. DC_C66 has a good selectivity for CARM1 against PRMT1 (IC50=21 μM), PRMT6 (IC50= 47μM), and PRMT5[1].

  • CAS Number: 108181-00-6
  • MF: C28H22NO2+
  • MW: 404.48
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPI-0610

CPI-0610 is a potent, selective, and cell-active BET bromodomain inhibitor CPI-0610 inhibits BRD4-BD1 with IC50 of 39 nM in time-resolved fluorescence energy transfer (TR-FRET ) binding assay. IC50 value: 39 nMTarget: Bromodomains in vitro: CPI-0610 is about 6 times more potent against BET BD-2 than against BET BD-1. When tested on other members of the bromodomain family, CPI-0610 is remarkably selective, displaying essentially no activity in TR-FRET- or AlphaLisa-based assays against the bromodomains of CBP, BRD9, BRPF1, PCAF, BRG1, ATAD2, TRIM24, BRD8 (IC50 of >20 μM, >80 μM, >20 μM, >20 μM, >20 μM, >80 μM, >20 μM, and >15 μM, respectively), among others. In a CEREP express panel of about 50 GPCRs, ion channels, and transporters, the compound displayed no meaningful inhibition. CPI-0610 also displays negligible inhibition of cytochrome P450 activity when tested at 10 μM against a number of common isoforms, and it also showed no time-dependent inhibition.[1] in vivo: The t1/2 of CPI-0610 for the rat and dog is 0.93 and 9 h, respectively.[1]

  • CAS Number: 1380087-89-7
  • MF: C20H16ClN3O2
  • MW: 365.813
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 622.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.5±31.5 °C

EI1

EI1 is a potent and selective EZH2 inhibitor with IC50 of 15 nM and 13 nM for EZH2 (WT) and EZH2 (Y641F), respectively.

  • CAS Number: 1418308-27-6
  • MF: C23H26N4O2
  • MW: 390.478
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 675.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.6±31.5 °C

HC Toxin

HC-Toxin, a cyclic tetrapeptide, is a potent HDAC inhibitor with an IC50 of 30 nM[1]. HC-Toxin induces tumor cell apoptosis and has anticancer effects[2].

  • CAS Number: 83209-65-8
  • MF: C21H32N4O6
  • MW: 436.50
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 819.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 449.2±34.3 °C

coumarin-SAHA

Coumarin-SAHA is a fluorescent probe for determining the binding affinities (kd) and the dissociation off-rates (koff) of the HDAC8-inhibitor complexes[1].

  • CAS Number: 1260635-77-5
  • MF: C18H22N2O5
  • MW: 346.378
  • Catalog: Histone Acetyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-16

PRMT5-IN-16 (Compound 20) is a PRMT5 inhibitor with anti-tumor activity. PRMT5 is a type of protein arginine methyltransferase, and is a new anti-tumor target related to epigenetic modification[1].

  • CAS Number: 2755304-16-4
  • MF: C25H34N8O2
  • MW: 478.59
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-21

JAK-IN-21 (Example 4) is a selective and potent JAK inhibitor with IC50s of 1.73, 2.04, 109 and 62.9 nM against JAK1, JAK2, J2V617F and TYK2, respectively[1].

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

C 21

C21 is a potent, irreversible, and selective PRMT1 inhibitor with an IC50 of 1.8 μM. C21 inhibits PRMT6 with an IC50 of 8.8 μM[1].

  • CAS Number: 1229236-78-5
  • MF: C90H161ClN36O24
  • MW: 2166.92
  • Catalog: Histone Methyltransferase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSD3-IN-2

NSD3-IN-2 is a potent NSD3 inhibitor with an IC50 value of 17.97 μM. NSD3-IN-2 inhibits the growth and proliferation of non-small cell lung cancer cell lines H460, H1299 and H1650 with anti-cancer activity[1].

  • CAS Number: 675190-57-5
  • MF: C17H15N5OS
  • MW: 337.40
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIRIBEDIL HYDROCHLORIDE

Piribedil hydrochloride is a potent and orally active dopamine D2 and dopamine D3 agonist. Piribedil hydrochloride is also a α2-adrenoceptors antagonist. Piribedil hydrochloride can inhibit MLL1 methyltransferase activity (EC50: 0.18 μM). Piribedil hydrochloride has the potential for the research of parkinson's disease, circulatory disorders, cancers[1][2][3][4].

  • CAS Number: 78213-63-5
  • MF: C16H19ClN4O2
  • MW: 334.80100
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: 469.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 237.7ºC

4,8-Dimethoxy-1-vinyl-9H-β-carboline

Dehydrocrenatidine, a natural alkaloid, is a specific JAK inhibitor. Dehydrocrenatidine inhibits voltage-gated sodium channels and ameliorates mechanic allodia in a rat model of neuropathic pain[1][2].

  • CAS Number: 65236-62-6
  • MF: C15H14N2O2
  • MW: 254.284
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 491.8±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 174.9±17.6 °C

GSK1324726A

GSK1324726A is a novel, potent, and selective inhibitor of BET proteins with high affinity to BRD2 (IC50=41 nM), BRD3 (IC50=31 nM), and BRD4 (IC50=22 nM).

  • CAS Number: 1300031-52-0
  • MF: C25H23ClN2O3
  • MW: 434.915
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 707.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.6±32.9 °C

Ruboxistaurin-d6 hydrochloride

Ruboxistaurin-d6 (LY333531-d6) hydrochloride is the deuterium labeled Ruboxistaurin hydrochloride. Ruboxistaurin (LY333531) hydrochloride is an orally active, selective PKC beta inhibitor (Ki=2 nM). Ruboxistaurin hydrochloride exhibits ATP dependent competitive inhibition of PKC beta I with an IC50 of 4.7 nM. Ruboxistaurin hydrochloride inhibits PKC beta II with an IC50 of 5.9 nM[1][2].

  • CAS Number: 1794767-04-6
  • MF: C28H23D6ClN4O3
  • MW: 511.04
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A