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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Antibody-drug Conjugate >
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Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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HA-100 hydrochloride

HA-100 hydrochloride is a potent protein kinase inhibitor, with IC50s of 4 μM, 8 μM, 12 μM and 240 μM for cGMP-dependent protein kinase (PKG), cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and MLC-kinase, respectively. HA-100 hydrochloride also used as a ROCK inhibitor[1][2].

  • CAS Number: 141543-63-7
  • MF: C13H16ClN3O2S
  • MW: 313.80300
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: 497.4ºC at 760 mmHg
  • Melting Point: 252-254ºC
  • Flash Point: 254.6ºC

DC_517

DC_517 is a DNA methyltransferase 1 (DNMT1) inhibitor, with an IC50 and a Kd of 1.7 μM and 0.91 μM, respectively.

  • CAS Number: 500017-70-9
  • MF: C33H35N3O2
  • MW: 505.650
  • Catalog: DNA Methyltransferase
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 727.9±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 394.0±32.9 °C

HDAC1/6-IN-1

HDAC1/6-IN-1 (compound D7) is a potent multitarget inhibitor of GLP, HDAC6 and HDAC1, with IC50 values of 1.3, 13, and 89 nM, respectively. HDAC1/6-IN-1 can inhibit the methylation and deacetylation of H3K9 on protein level. HDAC1/6-IN-1 induces cancer cell apoptosis, G0/G1 cell cycle arrest, and blocks migration and invasion[1].

  • CAS Number: 2630989-02-3
  • MF: C32H45N7O4
  • MW: 591.74
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nicotinamide

Nicotinamide is a form of vitamin B3 that plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. Nicotinamide is an inhibitor of SIRT1.

  • CAS Number: 98-92-0
  • MF: C6H6N2O
  • MW: 122.125
  • Catalog: Sirtuin
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 257.7±32.0 °C at 760 mmHg
  • Melting Point: 128-131 °C(lit.)
  • Flash Point: 109.7±25.1 °C

PROTAC BRD4 Degrader-3

PROTAC BRD4 Degrader-3 (compound 1004.1) is an efficacious PROTAC BRD4 degrader[1].

  • CAS Number: 2313234-00-1
  • MF: C55H65F2N9O9S2
  • MW: 1098.29
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Targaprimir-96

Targaprimir-96 is a potent inhibitor of microRNA-96 (miR-96) processing. Targaprimir-96 selectively modulates miR-96 production in cancer cells and triggers apoptosis. Targaprimir-96 binds primary miR-96 (pri-miR-96) with low nanomolar affinity. Targaprimir-96 directly engages pri-miR-96 in breast cancer cells and is ineffective on healthy breast cells[1].

  • CAS Number: 1655508-14-7
  • MF: C77H102N18O7
  • MW: 1391.75
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TNKS1/2-IN-2

TNKS1/2-IN-2 (Compound 21) is a potent and selective tankyrases inhibitor. TNKS1/2-IN-2 exhibits IC50 values of 4 nM and 63 nM against TNK1 and TNK2 in the enzymatic assay, respectively. TNKS1/2-IN-2 inhibits proliferation of A549 and H292 cell lines with IC50 values of 39.5 nM and 12.8 nM, respectively. TNKS1/2-IN-2 can be used for the research of cancer[1].

  • CAS Number: 1498300-35-8
  • MF: C26H24F3N3O4
  • MW: 499.48
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T-448

T-448 is a specific and irreversible inhibitor of lysine-specific demethylase 1 (LSD1, an H3K4 demethylase), with an IC50 of 22 nM. T-448 enhances H3K4 methylation in primary cultured rat neurons[1].

  • CAS Number: 1597426-53-3
  • MF: C38H44N8O6S2
  • MW: 772.94
  • Catalog: Histone Demethylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FKBP12 PROTAC dTAG-13

FKBP12 PROTAC dTAG-13 (dTAG-13) is an in vivo-active heterobifunctional adation tag (dTAG) small molecule that engage FKBP12F36V and CRBN, selectively degrade FKBP12F36V in a CRBN-dependent manner in cells; causes rapid degradation of nuclear and cytoplasmic FKBP12F36V fusion chimeras, and an unexpected superior antiproliferative effect of pan-BET bromodomain degradation over selective BRD4 degradation, characterize immediate effects of KRASG12V loss on proteomic signaling, and demonstrate rapid degradation in vivo.

  • CAS Number: 2064175-41-1
  • MF: C57H68N4O15
  • MW: 1049.168
  • Catalog: Epigenetic Reader Domain
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1134.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 639.6±34.3 °C

CARM1-IN-3

CARM1-IN-3 (compound 17b) is a potent and selective co-activator associated arginine methyltransferase (CARM1) inhibitor with IC50 values of 0.07, >25 µM for CARM1 and CARM3, respectively[1].

  • CAS Number: 912970-67-3
  • MF: C24H32N4O2
  • MW: 408.54
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BET bromodomain inhibitor

BET bromodomain inhibitor is a potent BET inhibitor extracted from patent WO/2015/153871A2, compound example 11.

  • CAS Number: 1505453-59-7
  • MF: C24H20ClN5O2
  • MW: 445.90100
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRX3177

SRX3177 is a potent, triple BRD4/PI3K/CDK4/6 inhibitor with nanomolar potency against PI3Kα (IC50=79 nM), BRD4 bromodomains (BD1 and BD2) (IC50=33 nM and 89 nM, respectively), and CDK4/6 (IC50=2.5/3.3 nM).SRX3177 is capable of targeting BRD4, PI3K and CDK4/6 simultaneously, induces apoptosis and cell cycle arrest and has in vitro efficacy in mantle cell lymphoma, hepatocellular carcinoma and neuroblastoma models.SRX3177 has antitumor efficacy in in vivo xenograft models and is less toxic than the combination of agents that inhibit individual targets.

  • CAS Number: 2241237-51-2
  • MF: C31H32N6O4S
  • MW: 584.695
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bisindolylmaleimide III

Bisindolylmaleimide III is a potent and selective inhibitor of protein kinase C (PKC). Bisindolylmaleimide III selectively interacts with either PKCα or ribosomal S6 protein kinase 1 after activation of these kinases[1].

  • CAS Number: 137592-43-9
  • MF: C23H20N4O2
  • MW: 384.43
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 708.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.4±32.9 °C

BI-9321

BI-9321 is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].

  • CAS Number: 2387510-86-1
  • MF: C22H21FN4
  • MW: 360.43
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK046 (iBET-BD2)

GSK046 (iBET-BD2) is a selective and orally active inhibitor of BET, with IC50s of 264 nM (BRD2 BD2), 98 nM (BRD3 BD2), 49 nM (BRD4 BD2) and 214 nM (BRDT BD2), respectively[1].

  • CAS Number: 2474876-09-8
  • MF: C23H27FN2O4
  • MW: 414.47
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L002

L002 is a novel potent, specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 uM. L002 has weak inhibitory effects against PCAF and GCN5 (IC50s =35 and 34 µM, respectively) and is specific for p300 over a panel of additional acetyltransferases, deacetylases, and methyltransferases[1]. L002 blocks histone acetylation and p53 acetylation, and inhibits STAT3 activation[2].

  • CAS Number: 321695-57-2
  • MF: C15H15NO5S
  • MW: 321.348
  • Catalog: Histone Acetyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 459.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 231.9±31.5 °C

MZ-242

A novel potent, selective Sirt2 inhibitor with IC50 of 0.118 uM; displays no inhibitory activity against Sirt1 and Sirt 3 (IC50>100 uM).

  • CAS Number: 1862238-01-4
  • MF: C24H27N7O3S2
  • MW: 525.646
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LBH589 lactate

Panobinostat lactate is a potent and orally active non-selective HDAC inhibitor. Panobinostat lactate has antineoplastic activities. Panobinostat lactate effectively disrupts HIV latency. Panobinostat lactate induces cell apoptosis and autophagy. Panobinostat lactate can be used for the study of refractory or relapsed multiple myeloma[1][2][3][4][5].

  • CAS Number: 960055-56-5
  • MF: C24H29N3O5
  • MW: 439.50400
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD2492

BRD2492 is a highly potent, selective HDAC1/2 inhibitor (IC50=2/19 nM, respectively) that displays excellent selectivity versus HDAC3 (IC50=2.08 uM, ≥110-fold selectivity) and all other HDAC isoforms, increases caspase-3 activation.

  • CAS Number: 1821669-43-5
  • MF: C20H18N4O2
  • MW: 346.39
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SMYD3-IN-1

SMYD3-IN-1 (compound 29) is an irreversible and selective inhibitor of SMYD3 (SET and MYND domain containing 3), with an IC50 of 11.7 nM[1].

  • CAS Number: 2095160-79-3
  • MF: C28H31ClN4O3
  • MW: 507.02
  • Catalog: Histone Methyltransferase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD4-IN-4

BRD4-IN-4 (Compound 1) is a BRD4 inhibitor (IC50=6.83 μM). BRD4-IN-4 selectively inhibits MV4-11 cell line proliferation and arrests cell at G1 phase. BRD4-IN-4 can be used for research of MLL leukemia[1].

  • CAS Number: 304685-40-3
  • MF: C17H18N2O3S
  • MW: 330.40
  • Catalog: Epigenetic Reader Domain
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 559.0±56.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 291.8±31.8 °C

VPC-70063

VPC-70063 is a potent Myc-Max inhibitor with an IC50 value of 8.9 μM for Myc-Max transcriptional activity inhibition. VPC-70063 reduces UBE2C promotor activity and AR-V7 levels, and induces PARP cleavage. VPC-70063 induces apoptosis and blocks Myc-Max interactions with DNA. VPC-70063 can be used for researching anticancer[1].

  • CAS Number: 13571-44-3
  • MF: C16H12F6N2S
  • MW: 378.34
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aurora A inhibitor 1

Aurora A inhibitor 1 is a potent and selective inhibitor of Aurora A. Aurora A has been implicated in cancers of diverse histological origin and may possess oncogenic properties when overexpressed. Aurora A inhibitor 1 has the potential for the research of cancer diseases mediated by aurora a (extracted from patent WO2021147974A1, compound 49)[1].

  • CAS Number: 2677799-04-9
  • MF: C25H28ClF2N5O2
  • MW: 503.97
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS049

MS 049 is a potent, selective, and cell-active dual inhibitor of PRMT4 and PRMT6 with IC 50 of 34 nM and 43 nM respectively.target: PRMT4, PRMT6;IC 50: 34 nM (PRMT4 ), 43 nM (PRMT6 );In vitro: MS 049 reduces the H3R2me2a mark in HEK293 cells in a concentration dependent manner. MS 049 treatment (72 h exposure) inhibits endogenous PRMT4 methyltransferase activity in a concentration dependent manner resulting in reduced levels of cellular asymmetric arginine dimethylation of Med12 (Med12-Rme2a, IC50 = 1.4 ± 0.1 μM (n = 3)) in HEK293 cells.

  • CAS Number: 1502816-23-0
  • MF: C15H24N2O
  • MW: 248.364
  • Catalog: Histone Methyltransferase
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 352.6±37.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 167.0±26.5 °C

Compound 7

HDAC-IN-4 is a selective HDAC6 and HDAC10 inhibitor with pIC50s of 7.2 and 6.8 in BRET assay, respectively. Antitumoral activity[1].

  • CAS Number: 1252003-13-6
  • MF: C20H21N3O2
  • MW: 335.40
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

dBET57

dBET57 is a potent and selective heterobifunctional degrader of BRD4 based on the PROTAC technology, with a DC50/5h of 500 nM for BRD4BD1, and is inactive on BRD4BD2[1].

  • CAS Number: 1883863-52-2
  • MF: C34H31ClN8O5S
  • MW: 699.18
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MG149

MG149 is a selective and potent Tip60 inhibitor with IC50 of 74 uM, similar potentcy for MOF(IC50= 47 uM); little potent for PCAF and p300(IC50 >200 uM).IC50 value: 74/47 uM (Tip60/MOF) [1]Target: Tip60/MOFMG 149, at 200 μM, inhibited about 90% of Tip60 activity but had no inhibitory impact on p300 and PCAF. MG 149 was essentiallycompetitive with Ac-CoA and noncompetitive with the histone substrate. HAT inhibition studies with MG 149 demonstrated that both compounds inhibited the HAT activity of the nuclear extractsof different regions significantly (p < 0.05).

  • CAS Number: 1243583-85-8
  • MF: C22H28O3
  • MW: 340.45600
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Garcinol

Garcinol, a polyisoprenylated benzophenone harvested from Garcinia indica, exerts anti-cholinesterase properties towards acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 0.66 µM and 7.39 µM, respectively[1]. Garcinol also inhibits histone acetyltransferases (HATs, IC50= 7 μM) and p300/CPB-associated factor (PCAF, IC50 = 5 μM). Garcinol has anti-inflammatory and anti-cancer activity[2].

  • CAS Number: 78824-30-3
  • MF: C38H50O6
  • MW: 602.800
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 710.8±60.0 °C at 760 mmHg
  • Melting Point: 235-236ºC
  • Flash Point: 397.6±29.4 °C

ABBV-744

ABBV-744 is a highly BDII-selective BET bromodomain inhibitor, used in the research of inflammatory diseases, cancer, and AIDS.

  • CAS Number: 2138861-99-9
  • MF: C28H30FN3O4
  • MW: 491.55
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sirt2-IN-1

Sirt2-IN-1 (Compound 9) is a sirtuin 2 (Sirt2) inhibitor with an IC50 of 163 nM[1].

  • CAS Number: 1862238-00-3
  • MF: C28H27N7O2S2
  • MW: 557.69
  • Catalog: Sirtuin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A