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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CBB1003

CBB1003 is a novel histone demethylase LSD1 inhibitor with IC50 of 10.54 uM.IC50 value: 10.54 uM [1]Target: LSD1 inhibitorin vitro: Treatment of F9 cells with CBB1003 led to the activation of CHRM4 and SCN3A expression. Treatment of CBB1003 led to significant growth inhibition of mouse embryonic teratocarcinoma F9 cells. Treatment of mouse ES cells with CBB1003 and 1007 also led to substantial inhibition of the spherical growth of ES cells [1]. CBB1003 inhibited CRC cell proliferation and colony formation. In cultured CRC cells, inhibiting LSD1 activity by CBB1003 caused a decrease in LGR5 levels while overexpression of LGR5 reduced CBB1003-induced cell death [2].

  • CAS Number: 1379573-88-2
  • MF: C25H31N9O4
  • MW: 521.57200
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DY-46-2

DY-46-2 is a high potency and selectivity novel non-nucleoside DNA methyltransferase 3A (DNMT3A) inhibitor with an IC50 value of 0.39 μM[1].

  • CAS Number: 1105110-83-5
  • MF: C19H22N6O5S
  • MW: 446.48
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TH34

TH34, an HDAC6/8/10 inhibitor with IC50s of 4.6 μM, 1.9 μM, and 7.7 μM respectively, shows high selectivity over HDAC1/2/3[1].

  • CAS Number: 2196203-96-8
  • MF: C15H16N2O2
  • MW: 256.30
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pomiferin

Pomiferin, a flavonoid from the fruits of Maclura pomifera, acts as an potential inhibitor of HDAC, with an IC50 of 1.05 μM, and also potently inhibits mTOR (IC50, 6.2 µM).

  • CAS Number: 572-03-2
  • MF: C25H24O6
  • MW: 420.45400
  • Catalog: HDAC
  • Density: 1.314g/cm3
  • Boiling Point: 673.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.3ºC

Momelotinib-d2

Momelotinib-d2 (CYT387-d2) 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: 1619927-63-7
  • MF: C23H20D2N6O2
  • MW: 416.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC6-IN-26

HDAC6-IN-26 (compound 23) is a potent inhibitor of HDAC6[1].

  • CAS Number: 2991427-19-9
  • MF: C13H12N8O
  • MW: 296.29
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-1

JAK-IN-1 is a JAK1/2/3 inhibitor with IC50s of 0.26, 0.8 and 3.2 nM, respectively. JAK-IN-1 shows improved selectivity for JAK3 over JAK1.

  • CAS Number: 1334673-53-8
  • MF: C20H24N6O2
  • MW: 380.44
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZL0590

ZL0590 is a potent, orally active BRD4 BD1-selective inhibitor with an IC50 of 90 nM for human BRD4 BD1. ZL0590 exhibits significant anti-inflammatory activities[1].

  • CAS Number: 2230496-99-6
  • MF: C23H27F3N4O4S
  • MW: 512.55
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rucaparib camsylate

Rucaparib is an inhibitor of PARP with a Ki of 1.4 nM for PARP1, and also shows binding affinity to eight other PARP domains.

  • CAS Number: 1859053-21-6
  • MF: C29H34FN3O5S
  • MW: 555.661
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SID 3712249

SID 3712249 (MiR-544 Inhibitor 1) is an inhibitor of the biogenesis of microRNA-544 (miR-544). Target: MiR-544MiR-544 represses expression of mTOR, promoting tumor cell survival in a hypoxic environment. Inhibition of miR-544 processing with MiR-544 Inhibitor 1 caused apoptosis in triple negative breast cancer cells in response to hypoxic stress, sensitized their response to 5-fluorouracil, and blocked their growth after transplantion into immunodeficient mice. SID 3712249 (MiR-544 Inhibitor 1) is believed to bind directly to the precursor miRNA, blocking production of the mature microRNA and resulting in decreased miR-544, HIF-1α, and ATM transcripts. MiR-544 Inhibitor 1 was as selective and 25-fold more potent than a 2′-O-methyl RNA antagomir.

  • CAS Number: 522606-67-3
  • MF: C17H21N7
  • MW: 323.396
  • Catalog: MicroRNA
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 669.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 358.4±31.5 °C

7-Methoxyisoflavone

7-Methoxyisoflavone is an isoflavone derivative and also an activator of adenosine monophosphate-activated protein kinase (AMPK).

  • CAS Number: 1621-56-3
  • MF: C16H12O3
  • MW: 252.26500
  • Catalog: AMPK
  • Density: 1.24g/cm3
  • Boiling Point: 421.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 200.3ºC

PF-04577806

PF-04577806 is a potent, selective and ATP competitive PKC inhibitor. PF-04577806 shows potent inhibitory activity towards PKCα, PKCβI, PKCβII, PKCγ, and PKCθ with IC50s of 2.4 nM, 8.1 nM, 6.9 nM, 45.9 nM, and 29.5 nM, respectively. PF-04577806 can reverse retinal vascular leakage in diabetic rats[1].

  • CAS Number: 1072100-81-2
  • MF: C26H37N7O3
  • MW: 495.62
  • Catalog: PKC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 613.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 324.8±31.5 °C

SGI 1027

SGI-1027 is a DNA methyltransferase (DNMT) inhibitor, with IC50s of 7.5 μM, 8 μM, and 12.5 μM for DNMT3B, DNMT3A, and DNMT1 with poly(dI-dC) as substrate.

  • CAS Number: 1020149-73-8
  • MF: C27H23N7O
  • MW: 461.518
  • Catalog: DNA Methyltransferase
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: >280℃
  • Flash Point: N/A

PU-141

PU-141 is a potent, selective CBP/p300 inhibitor that inhibits SK-N-SH cell growth with GI50 of 0.48 uM; blocks growth of SK-N-SH neuroblastoma xenografts in mice, also reduces histone lysine acetylation in vivo at concentrations that block neoplastic xenograft growth.

  • CAS Number: 168334-34-7
  • MF: C14H9F3N2OS
  • MW: 310.294
  • Catalog: Histone Acetyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Filgotinib maleate

Filgotinib (maleate) is a selective and orally active JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM and 116 nM for JAK1, JAK2, JAK3 and TYK2, respectively. Filgotinib (maleate) can be used for rheumatoid arthritis (RA) and Crohn's disease research[1][2].

  • CAS Number: 1802998-75-9
  • MF: C25H27N5O7S
  • MW: 541.58
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPP

DPP is a Platinum(IV) complex, bearing pterostilbene-derived axial ligand. DPP inhibit the JAK2-STAT3 pathway in breast cancer (BC) cells with antiproliferative activity, and activates caspase-3 and cleaved poly ADP-ribose polymerase to induces apoptosis. DPP promotes the maturation and antigen presentation of dendritic cells, and exhibits in vivo safety[1].

  • CAS Number: 2668267-47-6
  • MF: C36H40Cl2N2O10Pt
  • MW: 926.70
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oclacitinib

Oclacitinib is a novel JAK inhibitor. Oclacitinib is most potent at inhibiting JAK1 (IC50=10 nM).

  • CAS Number: 1208319-26-9
  • MF: C15H23N5O2S
  • MW: 337.440
  • Catalog: JAK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Resveratrol

Resveratrol (SRT 501), a natural polyphenol that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has a wide spectrum of targets including mTOR, JAK, β-amyloid.

  • CAS Number: 501-36-0
  • MF: C14H12O3
  • MW: 228.243
  • Catalog: Bacterial
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 449.1±14.0 °C at 760 mmHg
  • Melting Point: 253-255°C
  • Flash Point: 222.3±14.7 °C

HDAC-IN-39

HDAC-IN-39 (compound 16c) is a potent HDAC inhibitor, with IC50 values of 1.07 μM (HDAC1), 1.47 μM (HDAC2), and 2.27 μM (HDAC3), respectively. HDAC-IN-39 also significantly inhibits microtubule polymerization. HDAC-IN-39 induces cell cycle arrest at the G2/M phase. HDAC-IN-39 displays promising anticancer activity against resistant cancer cells[1].

  • CAS Number: 2414046-33-4
  • MF: C27H26N4O4S
  • MW: 502.58
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Basroparib

Basroparib is a potent poly (ADP-ribose) polymerase (PARP) inhibitor, with antineoplastic activity[1].

  • CAS Number: 1858179-75-5
  • MF: C18H21F2N7O3
  • MW: 421.40
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIRT1/2/3-IN-1

SIRT1/2/3-IN-1 (compound 10) is a highly potent, selective and cell permeable inhibitor of SIRT1, SIRT2 and SIRT3, with IC50s of 0.54, 0.253, and 0.72 μM respectively. SIRT1/2/3-IN-1 (compound 10) can be used for research of cancer[1].

  • CAS Number: 2413212-06-1
  • MF: C46H63N9O8S2
  • MW: 934.18
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Decursinol angelate

Decursinol angelate, a cytotoxic and protein kinase C (PKC) activating agent from the root of Angelica gigas, possesses anti-tumor and anti-inflammatory activities[1][2].

  • CAS Number: 130848-06-5
  • MF: C19H20O5
  • MW: 328.359
  • Catalog: PKC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 469.4±45.0 °C at 760 mmHg
  • Melting Point: 93-94 ºC
  • Flash Point: 206.6±28.8 °C

JAK kinase-IN-1

JAK kinase-IN-1 (Example 1) is a JAK inhibitor. JAK kinase-IN-1 inhibits TYK2, JAK1, JAK2 and JAK3 with IC50 values of 4.2 nM, 32 nM, 27 nM, 3473 nM respectively[1].

  • CAS Number: 2698389-43-2
  • MF: C17H19F2N7OS
  • MW: 407.44
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-TNG260

(S)-TNG260 is an isomer of TNG260 (HY-153358). TNG260 is a CoREST selective deacetylase (CoreDAC) inhibitor. TNG260 inhibits HDAC1 with 10-fold selectivity over HDAC3. TNG260 causes HDAC1 inhibition and reverses anti-PD1 resistance driven by STK11 deletion. TNG260 reduces intratumoral infiltration of neutrophils. TNG260 exhibits immune-mediated cell killing.

  • CAS Number: 2935964-93-3
  • MF: C20H18FN3O2S
  • MW: 383.44
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EHMT2-IN-1

EHMT2-IN-1 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 disorder or cancer[1].

  • CAS Number: 2230849-55-3
  • MF: C18H23N7O
  • MW: 353.42
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-3

JAK3/BTK-IN-3 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-3 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147952A1, compound 009)[1]

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

LRRK2-IN-8

LRRK2-IN-8 is a LRRK2 inhibitor. LRRK2-IN-8 inhibits LRRK2 (wt) and LRRK2 (G2019) with IC50s lower than 10 nM, and inhibits TYK2 and NUAK1 with IC50s of 10-100 nM[1].

  • CAS Number: 2770269-44-6
  • MF: C16H12F2N6
  • MW: 326.30
  • Catalog: LRRK2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD 4770

BRD4770 is a novel G9a(EHMT2) inhibitor with EC50 of 5 uM (trimethylated H3K9 in PANC-1 cell).IC50 value: 5 uM (PANC-1 cell) [1]Target: G9a inhibitorBRD4770 activates the ATM pathway without inducing DNA damage, while the ATR pathway is not affected. BRD4770 is a novel probe for studying G9a and its role in cellular senescence.Treatment of 5 μM BRD4770 for 24 h decreased H3K9 trimethylation level by 23% in PANC-1 cells. BRD9539 also inhibits PRC2 activity.

  • CAS Number: 1374601-40-7
  • MF: C25H23N3O3
  • MW: 413.468
  • Catalog: Histone Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

bruneomycin

Streptonigrin (Bruneomycin), a natural product produced by Streptomyces flocculus, possesses both anti-tumor and anti-bacterial activity. Streptonigrin acts as a pan-PAD inhibitor with IC50s of 48.3±34.2 µM, 26.1±0.3 µM, 0.43±0.03 µM, and 2.5±0.4 µM for PAD1, PAD2, PAD3, and PAD4, respectively[1].

  • CAS Number: 3930-19-6
  • MF: C25H22N4O8
  • MW: 506.46400
  • Catalog: Cancer
  • Density: 1.54g/cm3
  • Boiling Point: 719ºC at 760mmHg
  • Melting Point: 301-303℃
  • Flash Point: 388.7ºC

UMB-136

A novel bromodomain BRD4 inhibitor that significantly induces HIV-1 reactivation; dramatically reversed HIV-1 latency at both low (2.5 uM) and high (5 uM) doses in multiple cell models of HIV-1 latency through promoting Tat-dependent transcriptional elongation and Tat-P-TEFb association; enhances the latency-reversing effects of PKC agonists (prostratin, bryostatin-1) in CD8-depleted PBMCs containing latent viral reservoirs.

  • CAS Number: 2109805-83-4
  • MF: C24H27N5O2
  • MW: 417.504
  • Catalog: HIV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A