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 >
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Butyrolactone 3

Butyrolactone 3 is a specifical small-molecule inhibitor of the histone acetyltransferase Gcn5 (IC50=100 μM), which has a high affinity to the Gcn5 enzyme comparable to that of its natural substrate, histone H3. Butyrolactone 3 shows weak inhibitory on CBP (IC50=0.5 mM)[1]

  • CAS Number: 778649-18-6
  • MF: C9H12O4
  • MW: 184.189
  • Catalog: Histone Acetyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 386.2±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 158.5±21.4 °C

Foenumoside B

Foenumoside B is a triterpene saponin isolated from Lysimachia foenum-graecum. Foenumoside B activates AMPK signaling, inhibits PPARγ-induced adipogenesis, and shifts lipid metabolism toward lipolysis. Foenumoside B can be used in the study of obesity and obesity-related metabolic diseases[1].

  • CAS Number: 877661-00-2
  • MF: C60H96O25
  • MW: 1217.39
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sotrastaurin

Sotrastaurin is a potent pan-PKC inhibitor, with Kis of 0.22 nM, 0.64nM, 0.95 nM, 1.8 nM, 2.1 nM and 3.2 nM for PKCθ, PKCβ, PKCα, PKCη, PKCδ and PKCε, respectively.

  • CAS Number: 425637-18-9
  • MF: C25H22N6O2
  • MW: 438.481
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

sodium (Z)-5-fluoro-2-methyl-1-[[4-(methylsulphinyl)phenyl]methylene]-1H-indene-3-acetate

Sulindac (sodium) (MK-231) is an orally active nonsteroidal anti-inflammatory agent. Sulindac (sodium) is used to reduce pain, swelling, and joint stiffness from arthritis. Sulindac is also used for the research of arthritis of the spine, gouty arthritis. Sulindac (sodium), as an immunomodulatory agent, can downregulate PD-L1 through the blockade of NF-κB signaling and modulates the response of pMMR colorectal cancer (CRC) to anti-PD-L1 immunotherapy, inhibits the development and progression of colorectal cancer CRC. Sulindac (sodium) also inhibits TGF-β1- induced epithelial-mesenchymal transition (EMT) and suppresses lung cancer cell migration and invasion via downregulation of SIRT1[1][2].

  • CAS Number: 63804-15-9
  • MF: C20H16FNaO3S
  • MW: 378.39200
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP-2-IN-1

PARP-2-IN-1 is a potent and selective PARP-2 inhibitor with an IC50 of 11.5 nM.

  • CAS Number: 2115698-83-2
  • MF: C21H19F4N5O3
  • MW: 465.40
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zebularine

Zebularine (NSC309132; 4-Deoxyuridine) is a DNA methyltransferase inhibitor; also an inhibitor of cytidine deaminase with a Ki of 0.95 μM.

  • CAS Number: 3690-10-6
  • MF: C9H12N2O5
  • MW: 228.202
  • Catalog: Autophagy
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 499.0±55.0 °C at 760 mmHg
  • Melting Point: 160-162?C
  • Flash Point: 255.6±31.5 °C

VTX-27

VTX-27 is a selective protein kinase C θ (PKC θ) inhibitor, with Kis of 0.08 nM and 16 nM for PKC θ and PKC δ.

  • CAS Number: 1321924-70-2
  • MF: C20H24ClFN6O
  • MW: 418.896
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 625.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.3±31.5 °C

ZIP

ZIP is a selective peptide inhibitor of PKMζ. ZIP injections can block the impairment in morphine conditioned place preference induced[1].

  • CAS Number: 863987-12-6
  • MF: C12H25N3S4Zn
  • MW: 405.016
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lorpucitinib

Lorpucitinib is a Gut-Restricted JAK Inhibitor for the research of Inflammatory Bowel Disease[1].

  • CAS Number: 2230282-02-5
  • MF: C22H28N6O2
  • MW: 408.50
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK3735967

GSK3735967 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 40 nM.

  • CAS Number: 2170136-86-2
  • MF: C25H31N7Os
  • MW: 477.631
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PBRM1-BD2-IN-8

PBRM1-BD2-IN-8 (compound 34) is a potent PBRM1 Bromodomain inhibitor (PBRM1-BD2 Kd=4.4 μM, PBRM1-BD2 IC50=0.16 μM; PBRM1-BD5 Kd=25 μM). PBRM1-BD2-IN-8 shows anti-cancer activity[1].

  • CAS Number: 2819989-75-6
  • MF: C15H13BrN2O
  • MW: 317.18
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPUY074020

CPUY074020 is a potent G9a inhibitor with an IC50 of 2.18 μM, and possesses anti-proliferative activity [1].

  • CAS Number: 902279-44-1
  • MF: C25H28N4O2
  • MW: 416.52
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE/HDAC-IN-1

COX-2-IN-23 (compound A10) is a potent both AChE and HDAC inhibitor with IC50 values of 0.12 and 0.23 nM. COX-2-IN-23 exhibits antioxidant activity and metal chelating properties. COX-2-IN-23 can be used in alzheimer's disease research[1].

  • CAS Number: 2414053-06-6
  • MF: C26H27ClN4O3
  • MW: 478.97
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Panicolin

Skullcapflavone I can be isolated from A. nallamalayana. Skullcapflavone I inhibits collagenase and elastase enzyme with IC50s of 106.74 μM and 186.70 μM. Skullcapflavone I has anticancer activities by down-regulating miR-23a[1].

  • CAS Number: 41060-16-6
  • MF: C17H14O6
  • MW: 314.29
  • Catalog: MicroRNA
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 573.6±50.0 °C at 760 mmHg
  • Melting Point: 254-256℃
  • Flash Point: 215.5±23.6 °C

Ubiquinone Q0

Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling[1][2][3].

  • CAS Number: 605-94-7
  • MF: C9H10O4
  • MW: 182.173
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 331.4±42.0 °C at 760 mmHg
  • Melting Point: 58-60 °C(lit.)
  • Flash Point: 148.6±27.9 °C

PARP/EZH2-IN-1

PARP/EZH2-IN-1 is a first-in-class dual PARP (IC50 6.87 nM) and EZH2 (IC50 36.51 nM) inhibitor for triple-negative breast cancer with wild-type BRCA.

  • CAS Number: 2687273-52-3
  • MF: C43H41FN8O5
  • MW: 768.83
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHZ868

CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

  • CAS Number: 1895895-38-1
  • MF: C22H19F2N5O2
  • MW: 423.415
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EPZ011989 (trifluoroacetate)

EPZ011989 trifluoroacetate is a potent, selective orally bioavailable EZH2 inhibitor with Ki < 3 nM for EZH2 wt and EZH2 Y646; 15-fold selectivity over EZH1 and >3000-fold selectivity over other HMTase.IC50 value: < 3 nM ( Ki for wt EZH2, EZH2 Y646)Target: EZH2 inhibitorIn vitro: EPZ011989 is also a specific EZH2 inhibitor with a >15-fold selectivity over EZH1 and >3000-fold selectivity relative to the Ki of 20 other histone methyltransferases (HMTs) tested. EPZ011989 also exhibits metabolic stability. Furthermore, EPZ011989 reduces cellular H3K27 methylation in the Y641F, mutant-bearing human lymphoma cell line, WSU-DLCL2, with an IC50 below 100 nM. This functional response translates to activity in a long-term proliferation assay where EPZ011989 demonstrates an average lowest cytotoxic concentration (LCC) in WSU-DLCL2 cells of 208 nM. In vivo: The LCC parameter, when corrected for plasma protein-binding, predicts an efficacious plasma level in mouse for EPZ011989 of 158 ng/mL. The pharmacokinetics in SCID mice following oral administration of 125, 250, 500, and 1000 mg/kg indicated that the 1000 mg/kg dose provided coverage over the LCC for 24 h, while the 250 and 500 mg/kg doses provided coverage over this value for approximately 8 h. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma.

  • CAS Number: 1598383-41-5
  • MF: C37H52F3N5O6
  • MW: 719.834
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pociredir

Pociredir (FTX-6058) is a potent, selective and orally active small-molecule inhibitor of embryonic ectoderm development (EED) with KD value of 0.163 nM. Pociredir (FTX-6058) can be used for the research of inflammatory or hemoglobinopathies, such as sickle cell disease (SCD) [1][2].

  • CAS Number: 2490674-02-5
  • MF: C22H18FN5O2
  • MW: 403.41
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PS-432

PS-432 is an allosteric inhibitor of PKCι and PKCζ with IC50 of 16.9 and 18.5 uM, respectively; has no inhibitory activity against PKCα, PKCβ, PKCδ and PKCθ nor the activity of related kinases such as PDK1, PKB/Akt, RSK1, MSK1 and Aurora A; inhibits the proliferation of the lung cancer cell lines A549 (IC50=14.8 ± 4.2 uM) and A427 (IC50=10.4± 0.3 uM) as well as androgen-independent prostate cancer cell line DU145 (IC50 = 20.8 ± 9.0 uM); well tolerated in vivo.

  • CAS Number: 2083630-26-4
  • MF: C25H19ClN2O5S
  • MW: 494.947
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 662.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.5±34.3 °C

CRA-026440 hydrochloride

CRA-026440 hydrochloride is a potent, broad-spectrum HDAC (HDAC) inhibitor. The Ki values against recombinant HDAC isoenzymes HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM respectively. CRA-026440 hydrochloride shows antitumor and antiangiogenic activities[1].

  • CAS Number: 847459-98-7
  • MF: C23H25ClN4O4
  • MW: 456.92
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DCLX069

DCLX069 is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC50 value of 17.9 µM. DCLX069 shows less active against PRMT4 and PRMT6. DCLX069 has anticancer effects[1].

  • CAS Number: 792946-69-1
  • MF: C20H25N3O2
  • MW: 339.431
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 515.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.8±30.1 °C

JAK1/TYK2-IN-1

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 (IC50 = 29 and 41 nM respectively).

  • CAS Number: 1883300-48-8
  • MF: C18H20F3N7O
  • MW: 407.39
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ506

AZ506 is a potent SMYD2 inhibitor with an IC50 of 17 nM. AZ506 inhibits SMYD2 methyltransferase activity in cells, leading to a decrease in the SMYD2-mediated methylation signal.

  • CAS Number: 2043321-54-4
  • MF: C33H40N6O
  • MW: 536.71
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phenanthridin-6(5H)-one

6(5H)-Phenanthridinone is a potent PARP-1 inhibitor and immunomodulator. 6(5H)-Phenanthridinone inhibits cell proliferation and can be used in cancer research[1].

  • CAS Number: 1015-89-0
  • MF: C13H9NO
  • MW: 195.22
  • Catalog: PARP
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 274.8±7.0 °C at 760 mmHg
  • Melting Point: 290-292 °C(lit.)
  • Flash Point: 158.7±3.1 °C

EPZ011989

EPZ011989 is a potent, selective orally bioavailable EZH2 inhibitor with Ki < 3 nM for EZH2 wt and EZH2 Y646; 15-fold selectivity over EZH1 and >3000-fold selectivity over other HMTase.IC50 value: < 3 nM ( Ki for wt EZH2, EZH2 Y646)Target: EZH2 inhibitorIn vitro: EPZ011989 is also a specific EZH2 inhibitor with a >15-fold selectivity over EZH1 and >3000-fold selectivity relative to the Ki of 20 other histone methyltransferases (HMTs) tested. EPZ011989 also exhibits metabolic stability. Furthermore, EPZ011989 reduces cellular H3K27 methylation in the Y641F, mutant-bearing human lymphoma cell line, WSU-DLCL2, with an IC50 below 100 nM. This functional response translates to activity in a long-term proliferation assay where EPZ011989 demonstrates an average lowest cytotoxic concentration (LCC) in WSU-DLCL2 cells of 208 nM. In vivo: The LCC parameter, when corrected for plasma protein-binding, predicts an efficacious plasma level in mouse for EPZ011989 of 158 ng/mL. The pharmacokinetics in SCID mice following oral administration of 125, 250, 500, and 1000 mg/kg indicated that the 1000 mg/kg dose provided coverage over the LCC for 24 h, while the 250 and 500 mg/kg doses provided coverage over this value for approximately 8 h. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma.

  • CAS Number: 1598383-40-4
  • MF: C35H51N5O4
  • MW: 605.810
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 756.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 411.4±32.9 °C

OUL 35

OUL35 (NSC39047) is a potent and selective inhibitor of ARTD10 (PARP-10), with an IC50 of 329 nM[1].

  • CAS Number: 6336-34-1
  • MF: C14H12N2O3
  • MW: 256.25700
  • Catalog: PARP
  • Density: 1.298g/cm3
  • Boiling Point: 488.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 257.9ºC

6-Gingerol

[6]-Gingerol is an active compound isolated from Ginger (Zingiber officinale Rosc), exhibits a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation.

  • CAS Number: 23513-14-6
  • MF: C17H26O4
  • MW: 294.386
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 453.0±35.0 °C at 760 mmHg
  • Melting Point: 30 - 32ºC
  • Flash Point: 159.0±19.4 °C

PARP1-IN-7

PARP1-IN-7 is an inhibitor of poly(ADP-ribose) polymerase-1 (PARP1) as an anticancer agent.

  • CAS Number: 2084112-75-2
  • MF: C24H23N5O
  • MW: 397.47
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tozasertib

Tozasertib is the inhibitor of Aurora A/B/C kinases with Kis of 0.6, 18, 4.6 nM, respectively.

  • CAS Number: 639089-54-6
  • MF: C23H28N8OS
  • MW: 464.586
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A