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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NRD167

NRD167 is a potent and selective SIRT5 inhibitor.

  • CAS Number: 2166487-23-4
  • MF: C34H46N6O6S
  • MW: 666.83
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antitumor agent-104

Antitumor agent-104 (Compound 9) is an antitumor agent by inhibiting DNA damage repair in tumors. Antitumor agent-104 inhibits PARP1 enzymatic activity and the PAR protein level. Antitumor agent-104 also inhibits the expression of CDK12[1].

  • CAS Number: 2245272-16-4
  • MF: C31H33FN6O3
  • MW: 556.63
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC ligand-1

HDAC ligand-1 is a HDAC ligand that can be used to synthesize PROTAC HDAC degraders[1].

  • CAS Number: 34840-28-3
  • MF: C7H8N2O
  • MW: 136.15
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kahweol

Kahweol is one of the consituents of the coffee from Coffea Arabica with anti-inflammatory anti-angiogenic, and anti-cancerous activities. Kahweol inhibits adipogenesis and increase glucose uptake by AMP-activated protein kinase (AMPK) activation. Kahweol induces apoptosis.

  • CAS Number: 6894-43-5
  • MF: C20H26O3
  • MW: 314.419
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 476.6±45.0 °C at 760 mmHg
  • Melting Point: 88-90 °C
  • Flash Point: 242.0±28.7 °C

Bocodepsin

Bocodepsin (OKI-179) is an orally active and selective HDAC inhibitor, with antitumor activity. Bocodepsin can be used for suppression on solid tumor and hematologic malignancies[1].

  • CAS Number: 1834513-65-3
  • MF: C26H39N5O6S2
  • MW: 581.75
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKCβII Peptide Inhibitor I

PKCβII Peptide Inhibitor I is a PKCβII inhibitor. PKCβII Peptide Inhibitor I shows cardioprotective effects in rat cardiac Ischemia/reperfusion injury model. PKCβII Peptide Inhibitor I also prevents vascular endothelial dysfunction[1].

  • CAS Number: 862502-26-9
  • MF: C61H94N12O19
  • MW: 1299.47000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EHMT2-IN-2

EHMT2-IN-2 is a potent EHMT inhibitor, with IC50s of all <100 nM for EHMT1 peptide, EHMT2 peptide and cellular EHMT2. Used in the research of blood disease or cancer[1].

  • CAS Number: 2230850-47-0
  • MF: C21H22N6O
  • MW: 374.44
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Target Protein-binding moiety 4

Target Protein-binding moiety 4 is a BRD4(1) inhibitor with an IC50 of 7.9 μM.

  • CAS Number: 1300019-38-8
  • MF: C20H17ClN4O3
  • MW: 396.83
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS177

MS177 (MS-177) is a potent and selective EZH2 degarder (PROTAC) based on EZH2 inhibitor C24 with CRBN ligand pomalidomide with DC50 of 0.2 uM in EOL-1 cells.MS177 effectively degraded cellular EZH2-PRC2, suppressed global H3K27me3 in leukaemia cells.MS177 exhibited half-maximal degradation concentration (DC50) values of 0.2 ± 0.1 μM and 1.5 ± 0.2 μM, and maximum degradation (Dmax) values of 82% and 68%, respectively, in EOL-1 and MV4;11 cells.MS177 efficiently suppresses EZH2-PRC2 functions, also efficiently induces Myc degradation in cancer cells, suppresses EZH2-PRC2 functions.MS177 efficiently induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest, which is more effective than EZH2 inhibitors. MS177 (i.p. injection, 50-1 g/kg) represses AML growth without apparent toxicity in PDX models.

  • CAS Number: 2225938-86-1
  • MF: C48H55N11O8
  • MW: 914.037
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tenacigenin B

Tenacigenin B is a steroid that can be isolated from the genus Alocasia. Tenacigenin B has anti-tumor effects on lymphoma via regulation of Aurora-A[1][2].

  • CAS Number: 80508-42-5
  • MF: C21H32O5
  • MW: 364.48
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 537.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 187.2±23.6 °C

GSK2646264

GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.1. GSK2646264 also inhibits other kinases with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin[1].

  • CAS Number: 1398695-47-0
  • MF: C24H26N2O2
  • MW: 374.48
  • Catalog: LRRK2
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 517.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 266.7±30.1 °C

XAV-939

XAV-939 is a tankyrase (TNKS) inhibitor and an indirect inhibitor of Wnt/β-catenin signaling, with IC50s of 5 and 2 nM for TNKS1 and TNKS2, respectively.

  • CAS Number: 284028-89-3
  • MF: C14H11F3N2OS
  • MW: 312.310
  • Catalog: PARP
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 429.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 213.4ºC

IQZ23

IQZ23 inhibits adipocyte differentiation via AMPK pathway activation. IQZ23 exerts a high efficacy in decreasing the triglyceride level (EC50=0.033 μM) in 3T3-L1 adipocytes. IQZ23 could be used for the research of obesity and related metabolic disorders[1].

  • CAS Number: 2415643-79-5
  • MF: C26H29N5O2
  • MW: 443.54
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS 436

MS436 is a new class of bromodomain inhibitor, exhibits potent affinity of an estimated Ki=30-50 nM for the BRD4 BrD1 and a 10-fold selectivity over the BrD2.

  • CAS Number: 1395084-25-9
  • MF: C18H17N5O3S
  • MW: 383.424
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 673.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 361.3±34.3 °C

L-2-Hydroxyglutaric acid disodium

L-2-Hydroxyglutaric acid disodium is an epigenetic modifier and putative oncometabolite in renal cancer. L-2-Hydroxyglutaric acid disodium can inhibit histone demethylases and hence promote histone methylation[1]. L-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase (Mi-CK) activity with Km and Ki of 2.52 mM and 11.13 mM, respectively[2].

  • CAS Number: 63512-50-5
  • MF: C5H6Na2O5
  • MW: 192.078
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >300ºC
  • Flash Point: N/A

UNC6934

UNC6934 is a potent and selective drug-like chemical probe to interrogate the function of NSD2-PWWP1 with Kd of 91 nM.UNC6934 disrupts the NSD2-PWWP1 interaction with H3K36me2 nucleosomes in U2OS cells as measured by a NanoBret assay with an IC50 of 1.09 ± 0.23 microM. UNC7145, a closely-related control compound, with an iso-propyl group replacing a cyclo-propyl group, is inactive by SPR and NanoBret assays.

  • CAS Number: 2561494-77-5
  • MF: C24H21N5O4
  • MW: 443.16
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tazemetostat hydrochloride

Tazemetostat (EPZ-6438) hydrochloride is a potent, selective and orally active EZH2 inhibitor with IC50 values of 11 and 16 nM for EZH2 peptide and nucleosome, respectively. Tazemetostat hydrochloride can be used for cancer research[1].

  • CAS Number: 1467052-84-1
  • MF: C34H45ClN4O4
  • MW: 609.20
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CEP-8983

CEP-8983 is a PARP-1 and PARP-2 inhibitor (IC50: 20 and 6 nM). CEP-8983 is an effective chemosensitizing agent, and can sensitize chemotherapy-resistant cell lines and subcutaneous xenografts to Temozolomide (HY-17364) and Camptothecin (HY-16560)[1].

  • CAS Number: 374071-46-2
  • MF: C18H14N2O3
  • MW: 306.31500
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Di-n-Amyl phthalate

Dipentyl phthalate is an endocrine-disrupting phthalate plasticizer. Dipentyl phthalate increases AMPK phosphorylation and decreases AKT1 phosphorylation and SIRT1 levels. Dipentyl phthalate reduces adrenocorticotropic hormone levels. Dipentyl phthalate is a testicular toxicant[1].

  • CAS Number: 131-18-0
  • MF: C18H26O4
  • MW: 306.40
  • Catalog: AMPK
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 357.0±10.0 °C at 760 mmHg
  • Melting Point: -55ºC
  • Flash Point: 188.8±8.5 °C

NN-390

NN-390 is a potent and selective HDAC6 inhibitor, with an IC50 of 9.8 nM. NN-390 penetrates the blood-brain barrier (BBB). NN-390 shows study potential in metastatic Group 3 MB (medulloblastoma)[1].

  • CAS Number: 2490284-25-6
  • MF: C17H16F4N2O4S
  • MW: 420.38
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Butyric acid-13C1

Butyric acid-13C1 is the 13C labeled Butyric acid. Butyric acid is a histone deacetylase (HDAC) inhibitor, with anti-tumor effects in several cancers.

  • CAS Number: 38765-83-2
  • MF: C313CH8O2
  • MW: 89.09780
  • Catalog: HDAC
  • Density: 0.975 g/mL at 25ºC
  • Boiling Point: 162ºC(lit.)
  • Melting Point: -6--3ºC(lit.)
  • Flash Point: 170 °F

AZ505

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

  • CAS Number: 1035227-43-0
  • MF: C29H38Cl2N4O4
  • MW: 577.54200
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Epigenetic factor-IN-1

Epigenetic factor-IN-1 (40569Z) is a epigenetic factor inhibitor. Epigenetic factor-IN-1 has strong binding effect on SIRT7. Epigenetic factor-IN-1 can be used for liver cancer research[1].

  • CAS Number: 2640673-56-7
  • MF: C32H34FN5O6S2
  • MW: 667.77
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3',4'-dimethoxyflavone

3',4'-Dimethoxyflavone is a lipophilic flavone, can be isolated from the leaves of Primula veris. 3',4'-Dimethoxyflavone can reduce the synthesis and accumulation of PARP and protect cortical neurones against cell death induced by Parthanatos. 3',4'-Dimethoxyflavone is also an aryl hydrocarbon receptor antagonist in human breast cancer cells. 3',4'-Dimethoxyflavone can promote the proliferation of human hematopoietic stem cells. 3',4'-Dimethoxyflavone has various biological activities, including antioxidant, anti-cancer, anti-inflammatory, anti-atherogenic, hypolipidaemic, and neuroprotective or neurotrophic effects[1][2][3][4].

  • CAS Number: 4143-62-8
  • MF: C17H14O4
  • MW: 282.29100
  • Catalog: PARP
  • Density: 1.242g/cm3
  • Boiling Point: 428.5ºC at 760 mmHg
  • Melting Point: 154-155°C
  • Flash Point: 190.6ºC

CHDI 00390576

CHDI-390576, a potent, cell permeable and CNS penetrant class IIa histonedeacetylase (HDAC) inhibitor with IC50s of 54 nM, 60 nM, 31 nM, 50 nM for class IIa HDAC4, HDAC5, HDAC7, HDAC9, respectively, shows >500-fold selectivity over class I HDACs (1, 2, 3) and ~150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform[1].

  • CAS Number: 1629729-98-1
  • MF: C19H13F4N3O2
  • MW: 391.32
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT5 inhibitor

SIRT5 inhibitor is a potent Human Sirtuin 5 deacylase inhibitor, with an IC50 of 0.11 μM.

  • CAS Number: 2166487-21-2
  • MF: C31H39FN6O6S2
  • MW: 674.81
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC EED degrader-2

PROTAC EED degrader-2 is a PROTAC targeting EED with a pKD of 9.27. PROTAC EED degrader-2 is a polycomb repressive complex 2 (PRC2) inhibitor (pIC50=8.11) targeting the EED subunit[1].

  • CAS Number: 2639882-69-0
  • MF: C50H58FN11O6S
  • MW: 960.13
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phosphate acceptor peptide

Phosphate acceptor peptide is a substrate for cAMP-dependent protein kinase (PKA). phosphate acceptor peptide is also a weak PKC inhibitor[1].

  • CAS Number: 93511-94-5
  • MF: C41H74N16O11
  • MW: 967.13
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

anacardic acid

Anacardic Acid, extracted from cashew nut shell liquid, is a histone acetyltransferase inhibitor, inhibits HAT activity of p300 and PCAF, with IC50s of ∼8.5 μM and ∼5 μM, respectively.

  • CAS Number: 16611-84-0
  • MF: C22H36O3
  • MW: 348.519
  • Catalog: Epigenetic Reader Domain
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 474.8±33.0 °C at 760 mmHg
  • Melting Point: 90-91℃
  • Flash Point: 255.1±21.9 °C

AR-13503

AR-13503 a ROCK/PKC inhibitor, inhibiting angiogenesis and enhancing retinal pigment epithelium (RPE) permeability. AR-13503 also inhibits the formation of aberrant neovascularization (NV) in oxygen-induced retinopathy (OIR) model in mice[1][2].

  • CAS Number: 1254032-16-0
  • MF: C19H19N3O2
  • MW: 321.37
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A