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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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

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

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

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

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

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

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

Nezulcitinib

Nezulcitinib (TD-0903) is an inhaled and lung-selective pan-Janus kinase (JAK) inhibitor. Nezulcitinib can be used for the research of COVID-19 associated acute lung injury and impaired oxygenation[1][2].

  • CAS Number: 2412496-23-0
  • MF: C30H37N7O2
  • MW: 527.66
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SD 1008

SD-1008 is a potent JAK inhibitor. SD-1008 inhibits tyrosyl phosphorylation of STAT3, JAK2 and Src. SD-1008 also reduces STAT3-dependent luciferase activity. SD-1008 enhances apoptosis induced by Paclitaxel in ovarian cancer cells via directly blocking the JAK-STAT3 signaling pathway[1].

  • CAS Number: 960201-81-4
  • MF: C18H19NO5
  • MW: 329.35
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine

3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine (Compound 7) is an inhibitor of protein kinases, with IC50s of 0.092, 0.26, 0.77 μM for PKC-α, ROCK, ASK1. 3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine shows potent cytotoxicity against PC-3 cancer cells with an IC50 value of 0.16 μM[1].

  • CAS Number: 2226941-29-1
  • MF: C28H24N4O4
  • MW: 480.51
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPTH2 hydrochloride

CPTH2 hydrochloride is a potent histone acetyltransferase (HAT) inhibitor. CPTH2 hydrochloride selectively inhibits the acetylation of histone H3 by Gcn5. CPTH2 hydrochloride induces apoptosis and decreases the invasiveness of a clear cell renal carcinoma (ccRCC) cell line through the inhibition of acetyltransferase p300 (KAT3B)[1][2].

  • CAS Number: 2108899-91-6
  • MF: C14H15Cl2N3S
  • MW: 328.260
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UNC669

UNC 669 is a potent antagonist of L3MBTL1(IC50=4.2 uM) and L3MBTL3(IC50=3.1 uM).IC50 value: 4.2 uM/3.1 uM (L3MBTL1/L3MBTL3) [1]Target: L3MBTL1/L3MBTL3

  • CAS Number: 1314241-44-5
  • MF: C15H20BrN3O
  • MW: 338.243
  • Catalog: Histone Methyltransferase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 458.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 230.8±28.7 °C

HDACs/mTOR Inhibitor 1

HDACs/mTOR Inhibitor 1 is a dual Histone Deacetylases (HDACs) and mammalian target of Rapamycin (mTOR) target inhibitor for treating hematologic malignancies, with IC50s of 0.19 nM, 1.8 nM, 1.2 nM and >500 nM for HDAC1, HDAC6, mTOR and PI3Kα, respectively. HDACs/mTOR Inhibitor 1 stimulates cell cycle arrest in G0/G1 phase and induce tumor cell apoptosis with low toxicity in vivo[1].

  • CAS Number: 2271413-06-8
  • MF: C28H38N8O5
  • MW: 566.65
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Reticuline

Reticuline, isolated from Litsea cubeba, shows anti-inflammatory effects through JAK2/STAT3 and NF-κB signaling pathways. Reticuline inhibits mRNA expressions of TNF-α, and IL-6 and reduces the phosphorylation levels of JAK2 and STAT3[1].

  • CAS Number: 485-19-8
  • MF: C19H23NO4
  • MW: 329.390
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 504.9±50.0 °C at 760 mmHg
  • Melting Point: 125-126ºC
  • Flash Point: 259.2±30.1 °C

11α-O-Tigloyl-12β-O-acetyltenacigenin B

11α-O-Tigloyl-12β-O-acetyltenacigenin B is an ester derivative of Tenacigenin B (HY-N1168), which is isolated from Garcinia cambogia (MTC). Tenacigenin B modulates the antitumor effects of Aurora-A in lymphoma.

  • CAS Number: 154022-51-2
  • MF: C28H40O7
  • MW: 488.61
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirt1/2-IN-1

Sirt1/2-IN-1 (Compound 7) is a SIRT1 and SIRT2 inhibitor with IC50 values of 1.81, 2.10 and 20.5 µg/mL against SIRT1, SIRT2 and SIRT3, respectively. Sirt1/2-IN-1 displays activity in hyperacetylation of α-tubulin protein with an IC50 of 32.05 µg/mL. Sirt1/2-IN-1 shows prominent anticancer activity[1].

  • CAS Number: 2402779-21-7
  • MF: C22H13ClN2OS2
  • MW: 420.93
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-d8

Momelotinib-d8 (CYT387-d8) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally acitve 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: 1619927-68-2
  • MF: C23H14D8N6O2
  • MW: 422.51
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bomedemstat ditosylate

Bomedemstat (IMG-7289) ditosylate is an oral and irreversible inhibitor of the epigenetically active lysine-specific demethylase 1 (LSD1) in mouse models of myeloproliferative neoplasms (MPNs). Bomedemstat can be used for the research of acute myelogenous leukemia (AML) and myelofibrosis (MF). Antineoplastic activity[1].

  • CAS Number: 1990504-72-7
  • MF: C42H50FN7O8S2
  • MW: 864.02
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dorsomorphin

Dorsomorphin is a potent and selective AMPK inhibitor, that is competitive with ATP, with Ki=109±16 nM in the absence of AMP.

  • CAS Number: 866405-64-3
  • MF: C24H25N5O
  • MW: 399.488
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pTH-Related Protein (1-40) (human, mouse, rat) trifluoroacetate salt

pTH-Related Protein (1-40) (human, mouse, rat) stimulates calcium uptake in rat intestinal cells through PTHR1 receptor and PKCα/β signaling pathways. pTH-Related Protein (1-40) up-regulates parathyroid hormone 1 receptor (PTHR1) protein, four transcellular calcium transporters, potential vanillin member 6 (TRPV6), calcium-binding protein-D9K (CaBP-D9k), sodium-calcium Exchanger 1 (NCX1) and plasma membrane calcium ATPase 1 (PMCA1)[1].

  • CAS Number: 120298-73-9
  • MF: C207H334N66O58
  • MW:
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC 694621

NSC 694621 is a potent PCAF inhibitor, with an IC50 of 5.71 µM (PCAF/H31-21). NSC 694621 exhibits good activity of inhibiting the proliferation of cancer cells[1].

  • CAS Number: 104857-29-6
  • MF: C13H10N2O2S
  • MW: 258.30
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FTX-6058

FTX-6058 is a potent and orally active inhibitor of Embryonic Ectoderm Development (EED). FTX-6058 can induce HbF protein expression in cell and murine models. FTX-6058 can be used for the research of select hemoglobinopathies, including sickle cell disease and β-thalassemia[1][2].

  • CAS Number: 2490676-18-9
  • MF: C22H18FN5O2
  • MW: 403.41
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A