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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Y02224

Y02224 is a BET inhibitor. It shows the reasonable antiproliferative effect on leukemia cells.

  • CAS Number: 1853988-48-3
  • MF: C20H17BrN2O4S
  • MW: 461.33
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromodomain IN-1

Bromodomain IN-1 is a Bromodomain inhibitor extracted from patent WO2016069578A1, compound 4 [1].

  • CAS Number: 1914120-48-1
  • MF: C22H23ClN4O3S
  • MW: 458.96
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protein Kinase C (19-31)

Protein Kinase C (19-31), a peptide inhibitor of protein kinase C (PKC), derived from the pseudo-substrate regulatory domain of PKCa (residues 19-31) with a serine at position 25 replacing the wild-type alanine, is used as protein kinase C substrate peptide for testing the protein kinase C activity. Protein kinase C (PKC) is involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins[1][2].

  • CAS Number: 121545-65-1
  • MF: C67H118N26O16
  • MW: 1543.82
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-44

HDAC-IN-44 is a HDAC inhibitor with the IC50 value of 61.2 nM. HDAC-IN-44 shows high anticancer activity towards multiple cancer cell lines[1].

  • CAS Number: 2414921-46-1
  • MF: C26H27BrN4O4
  • MW: 539.42
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMPK-IN-3

AMPK-IN-3 (compound 67) is a potent and selective AMPK inhibitor with IC50s of 60.7, 107 and 3820 nM for AMPK (α2), AMPK (α1) and KDR, respectively. AMPK-IN-3 inhibits AMPK does not affect cell viability or cause significant cytotoxicity in K562 cells. AMPK-IN-3 can be used in study of cancer[1].

  • CAS Number: 2417674-27-0
  • MF: C25H33N5O3
  • MW: 451.56
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BB-Cl-Amidine

BB-Cl-Amidine is a peptidylarginine deminase (PAD) inhibitor.

  • CAS Number: 1802637-39-3
  • MF: C26H26ClN5O
  • MW: 459.970
  • Catalog: Inflammation/Immunology
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

12-O-tetradecanoylphorbol-13-acetate

Phorbol 12-myristate 13-acetate (PMA), a phorbol ester, is a commonly used PKC activator.

  • CAS Number: 16561-29-8
  • MF: C36H56O8
  • MW: 616.825
  • Catalog: PKC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 698.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.1±25.0 °C

WAY-354574

WAY-354574 is an active molecule targeting deacetylase (Sirtuin) for the study of Huntington's disease (HD)[1].

  • CAS Number: 851873-40-0
  • MF: C20H23ClN2O3S
  • MW: 406.92622
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lin28-let-7a antagonist 1

Lin28-let-7a antagonist 1 shows a clear antagonistic effect against the Lin28-let-7a interaction with an IC50 of 4.03 μM for Lin28A-let-7a-1 interaction.

  • CAS Number: 2024548-03-4
  • MF: C31H29N5O7
  • MW: 583.59
  • Catalog: MicroRNA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DHAQ DIACETATE

Mitoxantrone diacetate is a potent topoisomerase II inhibitor. Mitoxantrone diacetate also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM. Mitoxantrone diacetate induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone diacetate shows antitumor activity[1][2][3][4]. Mitoxantrone diacetate also has anti-orthopoxvirus activity with EC50s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively[5].

  • CAS Number: 70711-41-0
  • MF: C24H32N4O8
  • MW: 504.53300
  • Catalog: Apoptosis
  • Density: 1.45g/cm3
  • Boiling Point: 805.7ºC at 760 mmHg
  • Melting Point: 203-5ºC
  • Flash Point: 441.1ºC

Valrubicin

Valrubicin is a chemotherapy agent, inhibits TPA- and PDBu-induced PKC activation with IC50s of 0.85 and 1.25 μM, respectively, and has antitumor and antiinflammatory activity.

  • CAS Number: 56124-62-0
  • MF: C34H36F3NO13
  • MW: 723.644
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 867.7±65.0 °C at 760 mmHg
  • Melting Point: 116-117ºC
  • Flash Point: 478.6±34.3 °C

BRD4 Inhibitor-18

BRD4 Inhibitor-18 is a highly potent BRD4 inhibitor with IC50 value of 110 nM. BRD4 Inhibitor-18 has a hydrophobic acetylcyclopentanyl side chain. BRD4 Inhibitor-18 can significantly suppress the proliferation of MV-4-11 cells with high BRD4 level. BRD4 Inhibitor-18 has apoptosis-promoting and G0/G1 cycle-arresting activity[1].

  • CAS Number: 2451219-73-9
  • MF: C26H26ClN3O3S
  • MW: 496.02
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-9

PRMT5-IN-9 is a novel PRMT5 inhibitor for treating cancer, with an IC50 of 0.01 μM.

  • CAS Number: 2691869-52-8
  • MF: C25H23F3N6O
  • MW: 480.48
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EZH2-IN-13

EZH2-IN-13 is a potent EZH2 inhibitor, for details please refer to compound 73 in patent WO2017139404. EZH2-IN-13 can be used to study cancers or precancerous lesions associated with EZH2 activity[1].

  • CAS Number: 1403255-41-3
  • MF: C34H45N5O3
  • MW: 571.75
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6-IN-6

HDAC6-IN-6 (compound 6a) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC50 of 0.025 μM. HDAC6-IN-6 exhibits strong inhibitory activity against Aβ1-42 self-aggregation and AChE, with IC50 values of 3.0 and 0.72 μM. HDAC6-IN-6 can enhance neurite outgrowth without significant neurotoxicity[1].

  • CAS Number: 2413603-10-6
  • MF: C20H15N3O2
  • MW: 329.35
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AN-9

Pivanex (AN-9), a derivative of Butyric acid, is an HDAC inhibitor with antimetastic and antiangiogenic properties. Pivanex down-regulates bcr-abl protein and enhances apoptosis[1].

  • CAS Number: 122110-53-6
  • MF: C10H18O4
  • MW: 202.24800
  • Catalog: Apoptosis
  • Density: 1.008g/cm3
  • Boiling Point: 249.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 113ºC

LSD1-IN-12

LSD1-IN-12 (compound 2) is a potent LSD1 inhibitor, with Ki values of 1.1 μM (LSD1), 61 μM (LSD2), 2.3 μM (MAO-A), and 3.5 μM (MAO-B), respectively[1].

  • CAS Number: 1228143-76-7
  • MF: C16H16N2O
  • MW: 252.31
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS023 hydrochloride

MS023 trihydrochloride is a potent, selective, and cell-active inhibitor of human type I protein arginine methyltransferases (PRMTs) inhibitor, with IC50s of 30, 119, 83, 4 and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively[1].

  • CAS Number: 2108631-19-0
  • MF: C17H28Cl3N3O
  • MW: 396.78
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Delphinidin chloride

Delphinidin chloride, an anthocyanidin, is isolated from berries and red wine. Delphinidin chloride shows endothelium-dependent vasorelaxation. Delphinidin chloride also can modulate JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells[1][2][3].

  • CAS Number: 528-53-0
  • MF: C15H11ClO7
  • MW: 338.697
  • Catalog: Apoptosis
  • Density: 1.3946 (rough estimate)
  • Boiling Point: 454.94°C (rough estimate)
  • Melting Point: >350ºC
  • Flash Point: N/A

HDAC-IN-29

HDAC-IN-29 (compound 13b) is a potent pan-HDAC inhibitor. HDAC-IN-29 shows antitumor activity[1].

  • CAS Number: 2695593-95-2
  • MF: C20H23N3O4S
  • MW: 401.48
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT5 inhibitor 4

SIRT5 inhibitor 4 (compound 11) is a potent, selective SIRT5 inhibitor with IC50 values of 26.4 and >400μM for SIRT5 and other SIRT subtype, respectively[1].

  • CAS Number: 708992-34-1
  • MF: C18H15N3O4S
  • MW: 369.39
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-38

HDAC-IN-38 (compound 13) is a potent HDAC inhibitor. HDAC-IN-38 shows similar micro-molar inhibitory activity toward HDAC1, 2, 3, 5, 6, and 8. HDAC-IN-38 increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy. HDAC-IN-38 also increases the level of histone acetylation (H3K14 or H4K5)[1].

  • CAS Number: 2408123-36-2
  • MF: C27H28ClN3O2
  • MW: 461.98
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET-IN-9

BET-IN-9 is a BET inhibitor extracted from patent WO2022012456A1, compound example 1[1].

  • CAS Number: 2758778-88-8
  • MF: C22H24N4O3
  • MW: 392.45
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RG-101

RG-101 is a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122. miR-122 is an important host factor for hepatitis C virus (HCV) replication[1].

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

INO-1001

INO-1001 is a potent and selective Poly (ADP-ribose) polymerase (PARP) inhibitor with an IC50 of 0.05-1 μM. INO-1001 is a potent enhancer of radiation sensitivity and enhances radiation-induced cell killing by interfering with DNA repair mechanisms, resulting in necrotic cell death[1]. INO-1001 has anti-tumor effects[2].

  • CAS Number: 501364-82-5
  • MF: C23H25N3O4S
  • MW: 439.52700
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurora A inhibitor 2

Aurora A inhibitor 2 (Compound 16h) is a potent Aurora A kinase inhibitor with an IC50 of 21.94 nM. Aurora A inhibitor 2 induces caspase-dependent apoptosis in MDA-MB-231 cells[1].

  • CAS Number: 2412144-74-0
  • MF: C24H26N6O3
  • MW: 446.50
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CW 008

CW 008, a derivative of pyrazole-pyridine, is a CREB or PKA pathway agonist. CW 008 also is a stem cell differentiating agent. CW 008 stimulates osteoblast differentiation of human MSCs and increases bone formation in ovariectomized mice. CW008 promotes osteogenesis by activating cAMP/PKA/CREB signaling pathway and inhibiting leptin secretion[1][2][3].

  • CAS Number: 1134613-19-6
  • MF: C21H14F2N6O2
  • MW: 420.372
  • Catalog: Epigenetic Reader Domain
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-29

PRMT5-IN-29 is a potent and orally active PRMT5 Inhibitor with an IC50 of 1.5 μΜ. PRMT5-IN-29 has the potential for advanced cancers research[1].

  • CAS Number: 2242788-69-6
  • MF: C18H20Cl3N5O5
  • MW: 492.74
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SP-2509

SP2509 is a potent and selective antagonist of lysine specific demethylase 1 (LSD1) with IC50 of 13 nM.

  • CAS Number: 1423715-09-6
  • MF: C19H20ClN3O5S
  • MW: 437.897
  • Catalog: Histone Demethylase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STO-609 (acetate)

STO-609 acetate is a selective and cell-permeable inhibitor of the Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), with Ki values of 80 and 15 ng/mL for recombinant CaM-KKα and CaM-KKβ, respectively. STO-609 acetate inhibits AMP-activated protein kinase kinase (AMPKK) activity in HeLa cell lysates with an IC50 ~0.02 g/ml.

  • CAS Number: 1173022-21-3
  • MF: C21H14N2O5
  • MW: 374.35
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A