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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LY3295668 (AK-01)

LY3295668 is a potent, orally active and highly specific Aurora-A kinase inhibitor, with Ki values of 0.8 nM and 1038 nM for AurA and AurB, respectively.

  • CAS Number: 1919888-06-4
  • MF: C24H26ClF2N5O2
  • MW: 489.95
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGP 53353

CGP-53353 (DAPH-7) is an potent PKC inhibitor with IC50s of 0.41 mM and 3.8 mM for PKCβII and PKCβI, respectively. CGP-53353 can inhibit glucose-induced cell proliferation and DNA synthesis in AoSMC and A10 cells. CGP-53353 can be used for researching atherosclerosis of diabetic patients[1].

  • CAS Number: 145915-60-2
  • MF: C20H13F2N3O2
  • MW: 365.33
  • Catalog: DNA/RNA Synthesis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EM127

EM127 (compound 11c) is a SMYD3 covalent inhibitor with high selectivity, high affinity (KD=13 μM) and site-specificity. EM127 effectively inhibits ERK1/2 phosphorylation and reduces transcriptional regulation of SMYD3 target genes. EM127 effectively and prolongedly impairs methyltransferase activity. EM127 can be used in cancer research, particularly in SMYD3 positive tumours[1].

  • CAS Number: 1886879-71-5
  • MF: C14H18ClN3O3
  • MW: 311.76
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bromodomain inhibitor-12 (edisylate)

Bromodomain inhibitor-12 edisylate (example 303) is a bromodomain inhibitor that can be used in the research of autoimmune and inflammatory diseases[1].

  • CAS Number: 2010124-27-1
  • MF: C30H44N4O11S2
  • MW: 700.82
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRMT7-IN-1

PRMT7-IN-1 (Compound 14) is a PRMT7 inhibitor with an IC50 of 2.1 μM. PRMT7-IN-1 shows anticancer activity against different cancer cells[1].

  • CAS Number: 2247753-73-5
  • MF: C23H22FN5O3
  • MW: 435.45
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2879552

GSK2879552 is an orally available, irreversible inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity.

  • CAS Number: 1401966-69-5
  • MF: C23H28N2O2
  • MW: 364.48100
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Teleocidin A1

Teleocidin A1 (Lyngbyatoxin A), a highly toxic skin irritant, is a potent activator of protein kinase C (PKC). Teleocidin A1 shows antiproliferative activity against HeLa cancer cells (IC50=9.2 nM)[1][2].

  • CAS Number: 70497-14-2
  • MF: C27H39N3O2
  • MW: 437.61700
  • Catalog: PKC
  • Density: 1.06 g/cm3
  • Boiling Point: 665.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 356ºC

OM-153

OM-153 is a potent tankyrase inhibitor with IC50s of 13 and 2 nM for tankyrase 1 and tankyrase 2, respectively. OM-153 shows inhibition of WNT/β-catenin signaling and proliferation in COLO 320DM[1].

  • CAS Number: 2406278-81-5
  • MF: C28H24FN7O2
  • MW: 509.53
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DC-BPi-11

DC-BPi-11 is an inhibitor of bromodomain PHD finger transcription factor (BPTF), with an IC50 value of 698 nM. DC-BPi-11 shows remarkable inhibition against leukemia cell proliferation[1].

  • CAS Number: 2758411-61-7
  • MF: C20H23N5O2S
  • MW: 397.49
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LB-205

A Zn2+-dependent pan-inhibitor of class I and class II HDACs with a long half-life (12h) in vivo; significantly enhances the migration of astrocytes and accelerates wound repair more effectively than SAHA and VPA; up-regulates the expression of NGF, phospho-TrkA, p-AKT, NF-κB, and Bcl-2, while down-regulates the expression of p75 NTR, phospho-JNK, and Bax.

  • CAS Number: 1113025-86-7
  • MF: C18H21N3O2S
  • MW: 343.445
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC BET Degrader-1

PROTAC BET Degrader-1 is a potent BET degrader based on PROTAC, decreasing BRD2, BRD3, and BRD4 protein levels at low concentration.

  • CAS Number: 2093386-22-0
  • MF: C44H45N11O9
  • MW: 871.9
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC JL 37

TCJL37 is a potent, selective, and orally bioavailable TYK2 inhibitor with a Ki of 1.6 nM. TCJL37 can be used for the research of inflammatory bowel diseases (IBD)[1].

  • CAS Number: 1258294-34-6
  • MF: C17H11ClF2N4O2
  • MW: 376.74
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/Akt/CREB activator 1

PI3K/Akt/CREB activator 1 (compound AE-18) is a potent, orally active PI3K/Akt/CREB activator. PI3K/Akt/CREB activator 1 promotes neuronal proliferation, induced differentiation of Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of primary hippocampal neurons through upregulating brain-derived neurotrophic factor via the PI3K/Akt/CREB pathway. PI3K/Akt/CREB activator 1 can be used in research of vascular dementia (VaD)[1].

  • CAS Number: 2708177-73-3
  • MF: C19H15F4NO3
  • MW: 381.32
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CG-200745

CG-200745 is a potent HDAC inhibitor, with IC50s of <3 μM for sensitive non-small cell lung cancer (NSCLC) cell lines. CG-200745 induces the accumulation of p53, promotes p53-dependent transactivation, and enhances the expression of proteins encoded by p53 target genes, MDM2 and p21 (Waf1/Cip1) in human prostate cancer cells[1]. CG-200745 attenuates phosphorylation of p38 MAPK in kidneys and it has a renoprotective effect by suppressing renal fibrosis and inflammation in a unilateral ureteral obstruction (UUO) mouse model[2].

  • CAS Number: 936221-33-9
  • MF: C24H33N3O4
  • MW: 427.53700
  • Catalog: MDM-2/p53
  • Density: 1.148±0.06 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

I-CBP112 hydrochloride

I-CBP112 hydrochloride is a selective inhibitor of CBP/P300 that directly binds their bromodomains (Kds = 142 and 625 nM, respectively). I-CBP112 significantly reduces the leukemia-initiating potential of MLL-AF9(+) acute myeloid leukemia cells in a dose-dependent manner in vitro and in vivo. I-CBP112 increases the cytotoxic activity of BET bromodomain inhibitor JQ1 as well as doxorubicin[1].

  • CAS Number: 2147701-33-3
  • MF: C27H37ClN2O5
  • MW: 505.046
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PBRM1-BD2-IN-5

PBRM1-BD2-IN-5 is a potent PBRM1 Bromodomain inhibitor with Kd values of 1.5 μM and 3.9 μM for PBRM1-BD2 and PBRM1-BD5, respectively, and an IC50 value of 0.26 μM for PBRM1-BD2. PBRM1-BD2-IN-5 reduces the binding of full-length PBRM1 within the PBAF complex in cell lysates to acetylated histone peptide. PBRM1-BD2-IN-5 can be used to research anticancer[1].

  • CAS Number: 2819989-61-0
  • MF: C15H13ClN2O
  • MW: 272.73
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HFY-4A

HFY-4A is a HDAC inhibitor. HFY-4A inhibits breast cancer cell proliferation, migration, and invasion, and induces cell apoptosis. HFY-4A induces immunogenic cell death (ICD). HFY-4A inhibits tumor growth in breast cancer xenograft mouse models[1].

  • CAS Number: 2094810-82-7
  • MF: C20H19N3O2
  • MW: 333.38
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KDM2/7-IN-1

KDM2/7-IN-1 (TC-E 5002) is a selective histone demethylase KDM2/7 subfamily inhibitor (IC50 values are 0.2, 1.2, 6.8, 55, 83, >100 and >120 μM for KDM7A, KDM7B, KDM2A, KDM5A, KDM4C, KDM6A and KDM4A respectively). KDM2/7-IN-1 inhibits growth of HeLa and KYSE-150 cancer cells in vitro[1].

  • CAS Number: 1453071-47-0
  • MF: C15H27NO4
  • MW: 285.37900
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 87 °C
  • Flash Point: N/A

Pacritinib hydrochloride

Pacritinib hydrochloride is a potent inhibitor of both wild-type JAK2 (IC50=23 nM) and JAK2V617F mutant (IC50=19 nM). Pacritinib hydrochloride also inhibits FLT3 (IC50=22 nM) and its mutant FLT3D835Y (IC50=6 nM). Pacritinib hydrochloride can be used for the research of acute myeloid leukemia (AML) and myelofibrosis (MF)[1][2][3].

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

Dot1L-IN-7

Dot1L-IN-7 (compound 25) is a potent and selective disruptor of telomeric silencing 1-like protein (DOT1L) inhibitor with an IC50 of 1.0 μM. Dot1L-IN-7 selectively killed Mixed Lineage Leukemia (MLL)-AF9 without showing any effect on the growth of E2A-HLF cells[1].

  • CAS Number: 2580940-76-5
  • MF: C23H27N9O2
  • MW: 461.52
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(3-Chlorophenyl)-2-(4-(4-chlorophenyl)-1-oxophthalazin-2(1H)-yl)acetamide

PARP-1-IN-2 (compound 11g) is a potent and BBB-penetrated PARP1 inhibitor, with an IC50 of 149 nM. PARP1-IN-2 shows significantly potent anti-proliferative activity against Human lung adenocarcinoma epithelial cell line A549. PARP1-IN-2 can induce A549 cells apoptosis[1].

  • CAS Number: 684234-55-7
  • MF: C22H15Cl2N3O2
  • MW: 424.28
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KT-531

KT-531 (KT531) is a potent, selective HDAC6 inhibitor with IC50 of 8.5 nM, displays 39-fold selectivity.

  • CAS Number: 2490284-18-7
  • MF: C17H14F4N2O4S
  • MW: 418.363
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-45

HDAC-IN-45 (Compound 14) is a small molecule HDAC inhibitor and has anticancer activity, also can forms a hydrogenbond with residue Y303. HDAC-IN-45 (Compound 14) has substantial inhibitory effects towards HDAC1, 2 and 3 isoforms with IC50 values of 0.108, 0.585 and 0.563 μM respectively[1].

  • CAS Number: 2421122-61-2
  • MF: C25H20ClFN8O
  • MW: 502.93
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4-BD1/2-IN-1

BRD4-BD1/2-IN-1 is a potent BRD4 inhibitor with IC50s of <100 nM for BRD4 BD-1 and BRD4 BD-2, respectively (US20150148375A1, compound 5)[1].

  • CAS Number: 1781219-19-9
  • MF: C21H14F2N4O2
  • MW: 392.36
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(3β,5α,6β)-Androstane-3,5,6-triol

5α-Androstane-3β,5,6β-triol is a neuroprotectant. 5α-Androstane-3β,5,6β-triol can remarkably reverse intracellular acidification and alleviate neuronal injury through the inhibition of AMPK signaling. 5α-Androstane-3β,5,6β-triol remarkably reduced the infarct volume and attenuated neurologic impairment in acute ischemic stroke models of middle cerebral artery occlusion in vivo[1].

  • CAS Number: 4725-51-3
  • MF: C19H32O3
  • MW: 308.456
  • Catalog: AMPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 430.1±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 193.1±20.5 °C

Aurora kinase inhibitor-9

Aurora kinase inhibitor-9 (compound 9d) is a potent AURKA/B dual aurora kinase inhibitor with IC50s of 0.093, 0.09 µM for Aurora A, Aurora B, respectively. Aurora kinase inhibitor-9 shows broad spectrum anti-proliferative activity[1].

  • CAS Number: 2419107-09-6
  • MF: C19H17Cl2N3O4S
  • MW: 454.33
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PBRM1-BD2-IN-4

PBRM1-BD2-IN-4 (compound 15) is a potent PBRM1 Bromodomain inhibitor with Kd values of 5.5 μM and 11.1 μM for PBRM1-BD2 and PBRM1-BD5, respectively, and an IC50 value of 0.2 μM for PBRM1-BD2. PBRM1-BD2-IN-4 can be used to research anticancer[1].

  • CAS Number: 2819989-60-9
  • MF: C15H13ClN2O
  • MW: 272.73
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BChE/HDAC6-IN-1

BChE/HDAC6-IN-1 is a potent and selective dual BChE/HDAC6 inhibitor with IC50 values of 4 and 8.9 nM, respectively. BChE/HDAC6-IN-1 ameliorates the cognitive impairment in an Aβ1–42-induced mouse model and has the potental for AD research[1].

  • CAS Number: 2925457-27-6
  • MF: C34H43N5O5
  • MW: 601.74
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deuruxolitinib

Deuruxolitinib (CTP-543), a deuterated Ruxolitinib, modulates the activity of JAK1/JAK2. Deuruxolitinib can be used for the research hair loss disorders (from patent WO2017192905A1, compound I)[1].

  • CAS Number: 1513883-39-0
  • MF: C17H10D8N6
  • MW: 314.41
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC/HSP90-IN-3

HDAC/HSP90-IN-3 (compound J5) is a potent and selective fungal Hsp90 and HDAC dual inhibitor, with IC50 values of 0.83 and 0.91 μM, respectively. HDAC/HSP90-IN-3 shows antifungal activity against azole resistant C. albicans. HDAC/HSP90-IN-3 can suppress important virulence factors and down-regulate drug-resistant genes ERG11 and CDR1[1].

  • CAS Number: 2700035-54-5
  • MF: C26H33N5O6
  • MW: 511.57
  • Catalog: Fungal
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A