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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OSS_128167

OSS_128167 is a selective SIRT6 inhibitor with IC50s of 89, 1578 and 751 μM for SIRT6, SIRT1 and SIRT2, respectively.

  • CAS Number: 887686-02-4
  • MF: C19H14N2O6
  • MW: 366.32
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KW-2449

KW-2449 is a multi-targeted kinase inhibitor of FLT3, ABL, ABLT315I and Aurora kinase with IC50s of 6.6, 14, 4 and 48 nM, respectively.

  • CAS Number: 1000669-72-6
  • MF: C20H20N4O
  • MW: 332.399
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 604.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 319.1±31.5 °C

AMI 1

AMI-1 is a potent, cell-permeable compound which inhibits protein arginine N-methyltransferases (PRMTs), including human PRMT1 (IC50 = 8.8μM) and yeast-Hmt1p (IC50 = 3.0μM), by blocking peptide-substrate binding.IC50 value: 8.8μM (human PRMT1), 3.0μM (yeast-Hmt1p)Target: human PRMT1, yeast-Hmt1pin vitro: AMI-1 suppresses the transcriptional coactivator activity of PRMT1 and PRMT4 and it inhibits HIV-1 RT polymerase (IC50 = 5.0μM). PRMT1 methylates histone H4, and is essential for other subsequent histone modifications.[1] AMI-1 is the most active nonpeptidic inhibitor reported to be selective against PRMT1. AMI-1 is a selective PRMT inhibitor with a bisanionic structure that is related to compounds known to generate pleiotropic interactions with many proteins, should be further optimized before exploring additional binding pockets. [2]in vivo: AMI-1 is administered intranasally to chronic AIPI rats to determine PRMT effects on asthmatic parameters. AMI-1 inhibited the expression of COX2 in TGF-β-stimulated cells. AMI-1 administered to AIPI rats reduced COX2 production and humoral immune response, and it abrogated mucus secretion and collagen generation.[1]

  • CAS Number: 20324-87-2
  • MF: C21H14N2Na2O9S2
  • MW: 548.453
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-2,2,6,6-d6

Momelotinib-2,2,6,6-d6 (CYT387-2,2,6,6-d6) is the deuterium labeled Momelotinib (HY-10961). Momelotinib has inhibitory activity for JAK1/JAK2[1][2].

  • CAS Number: 1619927-65-9
  • MF: C23H16D6N6O2
  • MW: 420.50
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1,2,3,4,5,6-HEXABROMOCYCLOHEXANE

Benzene hexabromide, a bromohydrocarbon, is a potent inhibitor of JAK2 tyrosine kinase autophosphorylation.

  • CAS Number: 1837-91-8
  • MF: C6H6Br6
  • MW: 557.536
  • Catalog: JAK
  • Density: 2.9±0.1 g/cm3
  • Boiling Point: 388.9±42.0 °C at 760 mmHg
  • Melting Point: 82-85°C
  • Flash Point: 183.4±22.6 °C

Rovadicitinib hydrochloride

Rovadicitinib hydrochloride is a JAK inhibitor with an IC50 value <20 nM. Rovadicitinib hydrochloride also exhibits anti-inflammatory activity[1][2].

  • CAS Number: 1948242-60-1
  • MF: C17H20ClN7
  • MW: 357.84
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPI-905

CPI-905 is a potent and selective EZH2 inhibitor with IC50 value of 39.5 nM.

  • CAS Number: 931078-17-0
  • MF: C18H20N2O5
  • MW: 344.36
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M-1211

M‑1121 is a covalent and orally active inhibitor of the menin-MLL interaction capable of achieving complete and persistent tumor regression[1].

  • CAS Number: 2377337-93-2
  • MF: C42H57FN6O6S
  • MW: 793.00
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sodium aurothiomalate

Aurothiomalate sodium is a potent and selective oncogenic PKCι signaling inhibitor. Aurothiomalate sodium inhibits tumor cell proliferation and not cell apoptosis. Aurothiomalate sodium is a potent thioredoxin reductase (TrxR) inhibitor. Aurothiomalate sodium, an anti-rheumatoid agent, exhibits potent anti-tumor activity[1][2][3].

  • CAS Number: 12244-57-4
  • MF: C4H3AuNa2O4S
  • MW: 390.07500
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY 6035

BAY-6035 is a potent, selective and substrate-competitive inhibitor of SMYD3. BAY-6035 inhibits methylation of MEKK2 peptide with an IC50 of 88 nM[1].

  • CAS Number: 2247890-13-5
  • MF: C22H28N4O3
  • MW: 396.48
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AES-135

AES-135, a hydroxamic acid-based HDAC inhibitor, prolongs survival in an orthotopic mouse model of pancreatic cancer. AES-135 inhibits HDAC3, HDAC6, HDAC8, and HDAC11 with IC50s ranging from 190-1100 nM[1].

  • CAS Number: 2361659-61-0
  • MF: C33H29F6N3O5S
  • MW: 693.66
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2′-Deoxy-5-nitrocytidine

2′-Deoxy-5-nitrocytidine is a DNA Methyltransferase inhibitor extracted from patent CN108498529A. 2′-Deoxy-5-nitrocytidine can be used for the research of cancer[1].

  • CAS Number: 69100-02-3
  • MF: C9H12N4O6
  • MW: 272.21
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT-IN-3

SIRT-IN-3 is a potent SIRT inhibitor, with an IC50 of 17 μM for SIRT1. SIRT-IN-3 shows about 4-fold and 14-fold selectivity for SIRT1 over SIRT2 and SIRT3, respectively (IC50 of 74 μM and 235 μM for SIRT2 and SIRT3, respectively)[1].

  • CAS Number: 1211-19-4
  • MF: C13H12N2O
  • MW: 212.24700
  • Catalog: Sirtuin
  • Density: 1.218g/cm3
  • Boiling Point: 413.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 203.8ºC

SirReal 2

SirReal2 is a potent, isotype-selective Sirt2 inhibitor with an IC50 value of 140 nM and has very little effect on the activities of Sirt3-5. SirReal2 leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1[1].

  • CAS Number: 709002-46-0
  • MF: C22H20N4OS2
  • MW: 420.550
  • Catalog: Sirtuin
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MI-538

MI-538 is an inhibitor of the interaction between menin and MLL fusion proteins with an IC50 of 21 nM.

  • CAS Number: 1857417-10-7
  • MF: C27H25F3N8OS
  • MW: 566.6
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

USP1-IN-1

USP1-IN-1 (Formula I) is a USP1 and PARP inhibitor (extracted from patent WO2021163530).

  • CAS Number: 2446480-97-1
  • MF: C27H25F3N8O
  • MW: 534.54
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cimigenol-3-O-alpha-L-arabinoside

Cimiracemoside C is an active component of Cimicifuga racemosa, activates AMPK, has the potential activity against diabetes[1].

  • CAS Number: 256925-92-5
  • MF: C35H56O9
  • MW: 620.814
  • Catalog: AMPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 740.3±60.0 °C at 760 mmHg
  • Melting Point: 258-260℃
  • Flash Point: 401.5±32.9 °C

Tenovin 6 Hydrochloride

Tenovin-6 Hydrochloride 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, 67 μM for SirT1, SirT2, and SirT3, respectively.

  • CAS Number: 1011301-29-3
  • MF: C25H35ClN4O2S
  • MW: 491.089
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-2,2,6,6-d4

Momelotinib-2,2,6,6-d4 (CYT387-2,2,6,6-d4) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally acitve and ATP-competitive JAK1/JAK2 inhibitor with IC50s of 11 nM and 18 nM, respectively[1][2].

  • CAS Number: 1619927-64-8
  • MF: C23H18D4N6O2
  • MW: 418.48
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK9311

GSK9311 is a potent inhibitor of the BRPF bromodomain with pIC50 values of 6.0 and 4.3 for BRPF1 and BRPF2, respectively.

  • CAS Number: 1923851-49-3
  • MF: C24H31N5O3
  • MW: 437.544
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP10-IN-2

PARP10-IN-2 is a potent mono‐ADP‐ribosyltransferase PARP10 inhibitor with an IC50 of 3.64 μM for human PARP10. PARP10-IN-2 reveals potent inhibition on PARP2 and PARP15 with IC50s of 27 μM and 11 μM for human PARP2 and human PARP15, respectively[1].

  • CAS Number: 1042780-52-8
  • MF: C14H10N2O2
  • MW: 238.24
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

procainamide

Procainamide is a specific and potent inhibitor of DNA methyltransferase 1 (DNMT1). Procainamide is a Class 1A antiarrhythmic agent. Procainamide has the potential for the research of cancer and arrhythmias[1][2].

  • CAS Number: 51-06-9
  • MF: C13H21N3O
  • MW: 235.32500
  • Catalog: Bacterial
  • Density: 1.06
  • Boiling Point: 421.8ºC at 760mmHg
  • Melting Point: 47°C
  • Flash Point: 208.9ºC

MAK683

EED inhibitor-1 is an EED inhibitor extracted from patent US20160176882 A1, compound example 2; has IC50s of 59, 89, 26 nM in EED Alphascreen binding, LC-MS and ELISA assay.

  • CAS Number: 1951408-58-4
  • MF: C20H17FN6O
  • MW: 376.39
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP/P300 bromodomain inhibitor-3

CBP/P300 bromodomain inhibitor-3 is a potent inhibitor of the CBP/P300 family of bromodomains. CBP/P300 bromodomain inhibitor-3 inhibits CBP (IC50=0.01-0.1 µΜ) and BRD4 (IC50=1-1000 µΜ) activity[1].

  • CAS Number: 2304416-91-7
  • MF: C27H31N3O4
  • MW: 461.55
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BI-1622

BI-1622 is an orally active, potent and highly selective HER2 (ERBB2) inhibitor, with an IC50 of 7 nM. BI-1622 shows greater than 25-fold selectivity over EGFR. BI-1622 shows high antitumor efficacy in vivo in xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable drug metabolism and pharmacokinetics profile[1].

  • CAS Number: 2681392-19-6
  • MF: C26H24N10O2
  • MW: 508.53
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M-525

M-525 is a first-in-class, highly potent, irreversible small-molecule inhibitor of the menin-MLL interaction with binding IC50 of 3.3 nM in FP assays; inhibits MV4;11 (MLL fusion) and HL60 (No MLL fusion) cell growth with IC50 of 2.7 and 2,000 nM, respectively; significantly down-regulates the expression of MEIS1, HOXA9 and HOXA11 genes in a dosedependent anner at ow nanomolar concentrations, also effectively suppresses the expression of MEIS1 and HOX genes in the MOLM-13 cell line at 3 nM.

  • CAS Number: 2173582-08-4
  • MF: C39H51FN6O5S
  • MW: 734.932
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tazemetostat de(methylene morpholine)-O-C3-O-C-COOH

Tazemetostat de(methylene morpholine)-O-C3-O-C-COOH (Compound 21b) is an EZH2 degrader and can be used for the research of lymphoma[1].

  • CAS Number: 2750350-39-9
  • MF: C34H43N3O7
  • MW: 605.72
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Diethyl 1-benzyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate

BML-278 is a SIRT1 activator (EC150: 1 μM). BML-278 increases H3K9 methylation and inhibits H3K9 acetylation in both the paternal and maternal pronucleus. BML-278 improves early embryonic development. BML-278 arrests the cell cycle at the G1/S phase, and reduces senescence in primary human mesenchymal cells. BML-278 reduces tubulin acetylation in U937 cells. BML-278 also increases mitochondrial density in murine C2C12 myoblasts[1][2].

  • CAS Number: 120533-76-8
  • MF: C24H25NO4
  • MW: 391.46
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Furamidine

Furamidine (DB75) is abisbenzamidine derivative and an antiparasite agent. Furamidine is a potent, reversible and competitive tyrosyl-DNA phosphodiesterase 1 (TDP-1) inhibitor. Inhibition of TDP-1 by Furamidine is effective both with single- and double-stranded DNA substrates but is slightly stronger with the duplex DNA. Furamidine is also a selective and cell-permeable protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC50 of 9.4 μM. Furamidine is selective for PRMT1 over PRMT5, PRMT6, and PRMT4 (CARM1) (IC50s of 166 µM, 283 µM, and >400 µM, respectively)[1][2][3].

  • CAS Number: 73819-26-8
  • MF: C18H16N4O
  • MW: 304.346
  • Catalog: Histone Methyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 482.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 245.6±31.5 °C

JAK1-IN-4

JAK1-IN-4 is a potent and selective JAK1 inhibitor, with IC50s of 85 nM, 12.8 μM and >30 μM for JAK1, JAK2, and JAK3, respectively. JAK1-IN-4 inhibits STAT3 phosphorylation in NCI-H 1975 cells (IC50, 227 nM)[1].

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