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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Lepzacitinib

Lepzacitinib is a Janus kinase inhibitor targeting to JAK 1/3. Lepzacitinib exhibits anti-inflammatory effect and inhibits atopic dermatitis and other skin diseases[1].

  • CAS Number: 2321488-47-3
  • MF: C18H21N5O3
  • MW: 355.39
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-3

PRMT5-IN-3 is a PRMT5 inhibitor that exhibits synthetic lethality to tumor cells but produce few side effects combined with DNA damaging agents.

  • CAS Number: 2159123-14-3
  • MF: C22H23F3N4O3
  • MW: 448.44
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SF2523

SF2523 is a highly selective and potent inhibitor of PI3K with IC50s of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.

  • CAS Number: 1174428-47-7
  • MF: C19H17NO5S
  • MW: 371.414
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-8

Tyk2-IN-8 (compound 10) is a selective TYK2 inhibitor, which binds to TYK2 catalytically active JH1 domain with an IC50 of 17 nM, used in the treatment of psoriasis[1].

  • Density: 1.46±0.1 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC EED degrader-1

PROTAC EED degrader-1 is a PROTAC targeting EED with a pKD of 9.02. PROTAC EED degrader-1 is a polycomb repressive complex 2 (PRC2) inhibitor (pIC50=8.17) targeting the EED subunit[1].

  • CAS Number: 2639882-72-5
  • MF: C55H60FN11O8S
  • MW: 1054.20
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BVT 948

BVT948 is a protein tyrosine phosphatase (PTP) inhibitor which can also inhibit several cytochrome P450 (P450) isoforms and lysine methyltransferase SETD8.

  • CAS Number: 39674-97-0
  • MF: C14H11NO3
  • MW: 241.24200
  • Catalog: Histone Methyltransferase
  • Density: 1.39g/cm3
  • Boiling Point: 400.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 196.2ºC

Euphorbiasteroid

Euphorbiasteroid is a tricyclic diperpene of Euphorbia lathyris L., inhibits tyrosinase, and increases the phosphorylation of AMPK, with anti-cancer, anti-virus, anti-obesity and multidrug resistance-modulating effect[1].

  • CAS Number: 28649-59-4
  • MF: C32H40O8
  • MW: 552.655
  • Catalog: AMPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 633.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.9±31.5 °C

3-TYP

3-TYP is a selective SIRT3 inhibitor, with an IC50 of 16 nM, more potent over SIRT1 (IC50=88 nM), SIRT2 (IC50=92 nM).

  • CAS Number: 120241-79-4
  • MF: C7H6N4
  • MW: 146.14900
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT5-IN-20

PRMT5-IN-20 is a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with anti-tumor activity[1].

  • CAS Number: 880813-30-9
  • MF: C21H21N3
  • MW: 315.41
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosifidancitinib

Fosifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Fociatinib is used in studies of allergies, asthma and autoimmune diseases[1].

  • CAS Number: 1237168-58-9
  • MF: C21H21FN5O7P
  • MW: 505.39
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 723.1±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 391.1±35.7 °C

JAK3-IN-9

JAK3-IN-9 is an orally active JAK3 inhibitor with IC50 value of 1.7 nM. JAK3-IN-9 is highly selective to the JAK3 signal path. JAK3-IN-9 is lowly toxic with high oral bioavailability, shows good anti-arthritis activity. JAK3-IN-9 can be used in autoimmune disease research[1].

  • CAS Number: 1430095-30-9
  • MF: C17H23N5O4S
  • MW: 393.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6 degrader-3

HDAC6 degrader-3 is a potent and selective HDAC6 degrader via ternary complex formation and the ubiquitin-proteasome pathway with a DC50 value of 19.4 nM. HDAC6 degrader-3 has IC50s of 4.54 nM and 0.647 μM for HDAC6 and HDAC1, respectively. HDAC6 degrader-3 causes strong hyperacetylation of α-tubulin[1].

  • CAS Number: 2785404-83-1
  • MF: C41H41F4N7O11
  • MW: 883.80
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ζ-Stat trisodium

ζ-Stat trisodium (NSC37044 trisodium) is a specific and atypical PKC-ζ inhibitor, with an IC50 of 5 μM. ζ-Stat trisodium can reduce melanoma cell lines proliferation and induce apoptosis, and has antitumor activity in vitro[1][2].

  • CAS Number: 31894-34-5
  • MF: C10H5Na3O10S3
  • MW: 450.31
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PFI-3

PFI-3 is a selective, potent and cell-permeable SMARCA2/4 bromodomain inhibitor with a Kd of 89 nM.

  • CAS Number: 1819363-80-8
  • MF: C19H19N3O2
  • MW: 321.373
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 528.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.4±30.1 °C

ZEN-3411

ZEN-3411 is a BET inhibitor with IC50s of 0.05, 0.05 and 0.06 μM for BRD4(BD1), BRD4(BD2) and BRD4(BD1BD2), respectively. ZEN-3411 can be used to form PROTACs to induce degradation of BRD4[1].

  • CAS Number: 1952264-36-6
  • MF: C21H20N4O2
  • MW: 360.41
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Remodelin hydrobromide

Remodelin HBr salt is a novel potent and selective inhibitor of the acetyl-transferase protein NAT10.IC50 value:Target: NAT10 inhibitorRemodelin can improve nuclear architecture, chromatin organization, and fitness of both human lamin A/C-depleted cells and HGPS-derived patient cells, and decrease markers of DNA damage in these cells. Using a combination of chemical, cellular, and genetic approaches, acetyl-transferase protein NAT10 was identified as the target of Remodelin that mediated nuclear shape rescue in laminopathic cells via microtubule reorganization. Down-regulation and mutations of the nuclear-architecture proteins lamin A and C cause misshapen nuclei and altered chromatin organization associated with cancer and laminopathies, including the premature-aging disease Hutchinson-Gilford progeria syndrome (HGPS). Remodelin is a useful chemical tool to study how NAT10 affects nuclear architecture and suggest alternative strategies for treating laminopathies and aging.

  • CAS Number: 1622921-15-6
  • MF: C15H15BrN4S
  • MW: 363.275
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirt1/2-IN-3

Sirt1/2-IN-3 (compound PS9) is a dual inhibitor of SIRT1/2 with IC50s of 1.4 μM (SIRT1) and 2.0 μM (SIRT2), respsectivley. Sirt1/2-IN-3 completely blocks p53 deacetylation, and increase of p53 and α-tubulin acetylation. Sirt1/2-IN-3 induces apoptosis and shows anti-proliferation activity against human leukemia cell lines[1].

  • CAS Number: 301313-42-8
  • MF: C17H14ClNO4S
  • MW: 363.82
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-9

Tyk2-IN-9 is a potent,selective and specific inhibitor of JAK kinases, inhibits Tyk2, JAK1 and JAK2 with IC50 values of 6 nM, 21nM and 6nM, respectively. Tyk2-IN-9, example 19, is extracted from patent US2017240552A1[1].

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

Sirt1/2-IN-2

Sirt1/2-IN-2 (compound hsa55) is a dual inhibitor of SIRT1/2 with IC50s of 1.8 μM (SIRT1) and 2.4 μM (SIRT2), respsectivley. Sirt1/2-IN-2 completely blocks p53 deacetylation, and increase of p53 and α-tubulin acetylation. Sirt1/2-IN-2 induces apoptosis and shows anti-proliferation activity against human leukemia cell lines[1].

  • CAS Number: 670267-73-9
  • MF: C18H14N4O3S2
  • MW: 398.46
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Carboxycinnamic acid bishydroxamide

m-Carboxycinnamic acid bishydroxamide is a potent HDAC inhibitor, exhibiting ID50 values of 10 and 70 nM in vitro for HDAC1 and HDAC3, respectively[1]. m-Carboxycinnamic acid bishydroxamide also induces apoptosis and suppresses tumor growth[2].

  • CAS Number: 174664-65-4
  • MF: C10H10N2O4
  • MW: 222.20
  • Catalog: HDAC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CBP/p300-IN-10

CBP/p300-IN-10 is a highly potent histone acetyltransferase EP300 and CREBBP with IC50 values of 26 nM and 39 nM, respectively. CBP/p300-IN-10 can be used to research anticancer[1].

  • CAS Number: 2259641-71-7
  • MF: C25H24F5N5O3
  • MW: 537.48
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

E-7449

E7449 is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC50s of 2.0, 1.0, ∼50 and ∼50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using 32P-NAD+ as substrate.

  • CAS Number: 1140964-99-3
  • MF: C18H15N5O
  • MW: 317.345
  • Catalog: PARP
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 381.4±34.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 184.5±25.7 °C

GSK4028

GSK4028 is the enantiomeric negative control of GSK4027, which is a PCAF/GCN5 bromodomain chemical probe, the pIC50 of GSK4028 is 4.9 in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay.

  • CAS Number: 2079886-19-2
  • MF: C17H21BrN4O
  • MW: 377.28
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dTRIM24

dTRIM24 is a selective bifunctional degrader of TRIM24 based on PROTAC.

  • CAS Number: 2170695-14-2
  • MF: C55H68N8O13S2
  • MW: 1113.3
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPI-1328

CPI-1328 is an EZH2 inhibitor with a Ki value of 63 fM.

  • CAS Number: 2390367-27-6
  • MF: C28H36ClN3O4S
  • MW: 546.12
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α-Hydroxyglutaric acid-d4 disodium

α-Hydroxyglutaric acid-d4 (disodium) is the deuterium labeled α-Hydroxyglutaric acid disodium[1]. α-Hydroxyglutaric acid (2-Hydroxyglutarate) disodium is an α-hydroxy acid form of glutaric acid. α-Hydroxyglutaric acid disodium is a competitive inhibitor of multiple α-ketoglutarate-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases[2].

  • CAS Number: 2483831-91-8
  • MF: C5H2D4Na2O5
  • MW: 196.10
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKC Substrate 2

Protein kinase C substrate is a substrate of Protein kinase C, can be used to detect protein. Protein kinase C is a key regulatory element in signal transduction and exerts its effects by catalysing specific substrate phosphorylation[1].

  • CAS Number: 105802-82-2
  • MF: C51H100N22O11
  • MW: 1197.48000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-046

GDC-046 is a potent, selective, and orally bioavailable TYK2 inhibitor with Kis of 4.8, 0.7, 0.7, and 0.4 nM for TYK2, JAK1, JAK2, and JAK3, respectively[1].

  • CAS Number: 1258292-64-6
  • MF: C16H13Cl2N3O2
  • MW: 350.199
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 518.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.1±30.1 °C

Sirtuin-1 inhibitor 1

Sirtuin-1 inhibitor 1 (Compound 8) is an inhibitor of Sirtuin-1 that plays important roles in obesity-induced diabetes and aging-related diseases[1].

  • CAS Number: 945114-10-3
  • MF: C20H17N3O2
  • MW: 331.37
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

phenformin

Phenformin (1-phenethylbiguanide) is an orally active antidiabetic and anticancer agent. Phenformin has an incidence of associated lactic acidosis. Phenformin acts through acting AMPK activation and blocking mTOR pathway. Phenformin is also a substrate of P-glycoprotein (P-gp), and an OXPHOS inhibitor. Phenformin induces cancer cell apoptosis[1][2].

  • CAS Number: 114-86-3
  • MF: C10H15N5
  • MW: 205.260
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 332.2±35.0 °C at 760 mmHg
  • Melting Point: 280-282°C
  • Flash Point: 154.7±25.9 °C