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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BI 2536

BI 2536 is a dual PLK1 and BRD4 inhibitor with IC50s of 0.83 and 25 nM, respectively.

  • CAS Number: 755038-02-9
  • MF: C28H39N7O3
  • MW: 521.654
  • Catalog: Polo-like Kinase (PLK)
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Simmiparib

Simmiparib is a novel potent, orally active PARP1/2 inhibitor with IC50 of 1.75/0.22 nM, inhibits PARP1 >90-fold more potently than the other PARPs (PARP3, TNKS1, TNKS2); selectively induces the accumulation of DNA double-strand breaks, G2/M arrest and apoptosis in homologous recombination repair (HR)-deficient cells; potentiates the proliferative inhibition of several conventional anticancer drugs, reduces the poly(ADP-ribose) formation in HR-deficient cancer cells and xenografts; exhibits 10-fold greater growth inhibition than olaparib against HR-deficient human cancer cell- or tissue-derived xenografts in nude mice. Solid Tumors Phase 1 Clinical

  • CAS Number: 1551355-46-4
  • MF: C23H18F4N6O2
  • MW: 486.431
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4-BD1-IN-2

BRD4-BD1-IN-2 is a selective BRD4-BD1 inhibitor, with an IC50 of 2.51 µM (20-times greater than that of BD2). BRD4-BD1-IN-2 can be used in studies of cancer and cardiovascular diseases[1].

  • CAS Number: 2761321-26-8
  • MF: C20H15Br3N4O2
  • MW: 583.07
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BMS-986158

BMS-986158 is an inhibitor of the bromodomain and extra-terminal (BET) proteins.

  • CAS Number: 1800340-40-2
  • MF: C30H33N5O2
  • MW: 495.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD-6929

BRD-6929 (Cpd-60) is a brain-penetrant, selective inhibitor of HDAC1 and HDAC2 (IC50= 1 and 8 nM), extracted from patent US2018360927[1]. BRD-6929 (Cpd-60) shows high-affinity to HDAC1 and HDAC2 with Ki of 0.2 and 1.5 nM, respectively[2]. BRD-6929 (TPB) potentiates the efficacy of gnidimacrin (a PKC Agonist) against latent HIV-1[3].

  • CAS Number: 849234-64-6
  • MF: C19H17N3O2S
  • MW: 351.42200
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MTL-CEBPA

MTL-CEPBA is a small activating RNA targeting for upregulation of C/EBPα. MTL-CEPBA has anti-inflammatory and anti-cancer activity[1].

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

AJH-836

AJH-836 is an activator of Munc13-1 and PKC ε/α (Kd: 4.5 nM for PKCα) . AJH-836 triggers the translocation of Munc13-1 from the cytoplasm to the plasma membrane. AJH-836 can be used for research of neurodegenerative diseases[1].

  • CAS Number: 388621-67-8
  • MF: C22H38O5
  • MW: 382.53
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK621

GSK621 is a specific AMPK activator, with IC50 values of 13-30 μM for AML cells. GSK621 induces autophagy and apoptosis. GSK621 induces eiF2α phosphorylation-a hallmark of UPR activation[1].

  • CAS Number: 1346607-05-3
  • MF: C26H20ClN3O5
  • MW: 489.907
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PR5-LL-CM01

PR5-LL-CM01 is a novel selective, small-molecule inhibitor of PRMT5 methyltransferase with IC50 of 7.5 uM; displays >10-fold selectivity over PRMT3, and no inhibitory activity over PRMT1/4/6/8; exhibits cell viability inhibition with IC50 of 2-4 uM in PDAC cells, IC50 of 10-11 uM in CRC cells, more potent than EPZ015666; significantly inhibits NF-κB activation in PDAC and CRC cells, and shows dramatic anti-tumor efficacy in vivo.

  • CAS Number: 1005307-86-7
  • MF: C23H27N7
  • MW: 401.518
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SW-100

SW-100, a selective histone deacetylase 6 (HDAC6) inhibitor with an IC50 of 2.3 nM, shows at least 1000-fold selectivity for HDAC6 relative to all other HDAC isozymes. SW-100 displays a significantly improved ability to cross the blood-brain-barrier[1].

  • CAS Number: 2126744-35-0
  • MF: C17H17ClN2O2
  • MW: 316.78
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ruboxistaurin hydrochloride

Ruboxistaurin hydrochloride is a selective and ATP-competitive PKCβ inhibitor, with IC50s of 4.7 and 5.9 nM for PKCβI and PKCβII, shows less potent inhibition on PKCη (IC50, 52 nM), PKCα (IC50, 360 nM), PKCγ (IC50, 300 nM), PKCδ (IC50, 250 nM), and has no effect on PKCζ (IC50, >100 μM).

  • CAS Number: 169939-93-9
  • MF: C28H29ClN4O3
  • MW: 505.008
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CM-675

CM-675 is a dual phosphodiesterase 5 (PDE5) and class I histone deacetylases-selective inhibitor, with IC50 values of 114 nM and 673 nM for PDE5 and HDAC1, respectively. CM-675 has potential to treat Alzheimer’s disease[1].

  • CAS Number: 1872466-47-1
  • MF: C31H32N6O3
  • MW: 536.62
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-Acetamidophenol

Acetaminophen (paracetamol) is a selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 25.8 μM; is a widely used antipyretic and analgesic drug.

  • CAS Number: 103-90-2
  • MF: C8H9NO2
  • MW: 151.163
  • Catalog: Bacterial
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 387.8±25.0 °C at 760 mmHg
  • Melting Point: 168-172 °C(lit.)
  • Flash Point: 188.4±23.2 °C

Chelerythrine

Chelerythrine is a natural alkaloid, acts as a potent and selective Ca2+/phospholopid-dependent PKC antagonist, with an IC50 of 0.7 μM[1]. Chelerythrine has antitumor, antidiabetic and anti-inflammatory activity[2].

  • CAS Number: 34316-15-9
  • MF: C21H18ClNO4
  • MW: 348.371
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 195-205ºC
  • Flash Point: N/A

Sodium butyrate

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

  • CAS Number: 156-54-7
  • MF: C4H7NaO2
  • MW: 110.087
  • Catalog: Autophagy
  • Density: 0.987g/cm3
  • Boiling Point: 164.3ºC at 760 mmHg
  • Melting Point: 250-253 °C(lit.)
  • Flash Point: 69.7ºC

K-252a

K-252a, a staurosporine analog isolated from Nocardiopsis sp. soil fungi, inhibits protein kinase, with IC50 values of 470 nM, 140 nM, 270 nM, and 1.7 nM for PKC, PKA, Ca2+/calmodulin-dependent kinase type II, and phosphorylase kinase, respectively[1][2].

  • CAS Number: 99533-80-9
  • MF: C27H21N3O5
  • MW: 467.473
  • Catalog: PKC
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 685.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 368.2±31.5 °C

SRT 1720 dihydrochloride

SRT 1720 dihydrochloride is a selective and orally active activator of SIRT1 with an EC50 of 0.10 μM, and shows less potent activities on SIRT2 and SIRT3[1].

  • CAS Number: 2468639-77-0
  • MF: C25H25Cl2N7OS
  • MW: 542.48
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OXF BD 02

OXF BD 02 is a selective inhibitor of BRD4(1) (the first bromodomain of BRD4) with IC50value of 382 nM[1].

  • CAS Number: 1429129-68-9
  • MF: C18H17NO3
  • MW: 295.33
  • Catalog: Epigenetic Reader Domain
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 515.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 265.5±30.1 °C

CpG Methyltransferase

CpG Methyltransferase is a DNA methyltransferase. CpG Methyltransferase can methylate the C5 position on the base moiety of all cytosine nucleotides contained in unmethylated or hemimethylated double stranded DNA in a 5’-CpG-3’ context[1].

  • CAS Number: 1809633-78-0
  • MF:
  • MW:
  • Catalog: DNA Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RUBOXISTAURIN MESYLATE

Ruboxistaurin (LY333531) is an orally active, selective PKC beta inhibitor (Ki=2 nM). Ruboxistaurin exhibits ATP dependent competitive inhibition of PKC beta I with an IC50 of 4.7 nM. Ruboxistaurin inhibits PKC beta II with an IC50 of 5.9 nM[1][2].

  • CAS Number: 169939-94-0
  • MF: C28H28N4O3
  • MW: 468.54700
  • Catalog: PKC
  • Density: 1.34g/cm3
  • Boiling Point: 744.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 404ºC

OM-1700

OM-1700 is a potent tankyrase inhibitor with IC50s of 127 and 14 nM for tankyrase 1 and tankyrase 2, respectively. OM-1700 reduces cell growth in the colon cancer cell line COLO 320DM (GI50=650 nM)[1].

  • CAS Number: 2406276-78-4
  • MF: C25H23FN6O2
  • MW: 458.49
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

I-CBP 112

I-CBP112 is a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor, that targets the CBP/p300 bromodomains.

  • CAS Number: 1640282-31-0
  • MF: C27H36N2O5
  • MW: 468.585
  • Catalog: Epigenetic Reader Domain
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 623.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 330.9±31.5 °C

HL23

HL23 is a histone deacetylase (HDAC) inhibitor with activity against hepatocellular carcinoma (HCC). HL23 enhances acetylation of the TXNIP promoter and upregulates TXNIP expression, thereby mediating potassium channel activity and triggering TXNIP-dependent potassium deprivation. HL23 inhibits HCC progression and metastasis and has a synergistic effect with Sorafenib (HY-10201) and is more potent than Sorafenib+Vorinostat (HY-10221)[1].

  • CAS Number: 1448355-15-4
  • MF: C44H44N2O7
  • MW: 712.83
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Birabresib (OTX015)

Birabresib (OTX-015) is a potent bromodomain (BRD2/3/4) inhibitor with IC50s ranging from 92 to 112 nM.

  • CAS Number: 202590-98-5
  • MF: C25H22ClN5O2S
  • MW: 491.992
  • Catalog: Epigenetic Reader Domain
  • Density: 1.45±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3-IN-11

JAK3-IN-11 (Compound 12), a potent, noncytotoxic, irreversible, orally active JAK3 inhibitor with IC50 value of 1.7 nM, has excellent selectivity (>588-fold compared to other JAK isoforms), covalently bind to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T cell proliferation, is a promising tool for study autoimmune diseases[1].

  • CAS Number: 2412734-00-8
  • MF: C23H23N5O2
  • MW: 401.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCT241736

CCT241736 is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor, which inhibits Aurora kinases (Aurora-A Kd, 7.5 nM, IC50, 38 nM; Aurora-B Kd, 48 nM), FLT3 kinase (Kd, 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd, 38 nM) and FLT3(D835Y) (Kd, 14 nM).

  • CAS Number: 1402709-93-6
  • MF: C22H23Cl2N7
  • MW: 456.371
  • Catalog: Aurora Kinase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-632

TAK-632 is a potent pan-RAF inhibitor with IC50 of 1.4, 2.4 and 8.3 nM for CRAF, BRAFV600E, BRAFWT, respectively.

  • CAS Number: 1228591-30-7
  • MF: C27H18F4N4O3S
  • MW: 554.515
  • Catalog: Aurora Kinase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HISPIDIN

Hispidin, a PKC inhibitor and a phenolic compound from Phellinus linteus, has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti-dementia properties[1].

  • CAS Number: 555-55-5
  • MF: C13H10O5
  • MW: 246.21500
  • Catalog: PKC
  • Density: 1.657g/cm3
  • Boiling Point: 554.2ºC at 760 mmHg
  • Melting Point: 312-315ºC
  • Flash Point: 220.1ºC

SR-0813

SR-0813 is a potent and selective ENL/AF9 YEATS domain inhibitor. SR-0813 has IC50 and EC50 values of 25 nM and 205 nM for ENL YEATS domain, respectively. SR-0813 has IC50 and EC50 values of 311 nM and 76 nM (CETSA) for AF9 YEATS domain, respectively. SR-0813 binds MAP3K19 with over 100-fold lower affinity (Kd=3.5 μM) than ENL YEATS (Kd=30 nM). SR-0813 can be used for the research of acute leukemia[1].

  • CAS Number: 2597186-19-9
  • MF: C25H32N6O3S
  • MW: 496.62
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Aminoisoquinolin-1(2H)-one

5-AIQ (5-Aminoisoquinolin-1-one) is a water-soluble PARP-1 inhibitor. 5-AIQ is an important functional group in various drugs. 5-AIQ reduces the tissue injury associated with ischemia-reperfusion of the liver, it can be used for the research of the therapy conditions associated with ischemia-reperfusion of the liver[1][2].

  • CAS Number: 93117-08-9
  • MF: C9H8N2O
  • MW: 160.173
  • Catalog: PARP
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 477.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 242.4±28.7 °C