| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
EML 425 selectively targets the histone acetyltransferases CREB-binding protein (CBP) and p300. It inhibits these enzymes with IC₅₀ values of 2.9 µM for CBP and 1.1 µM for p300. As a non-competitive inhibitor, EML 425 is effective against both acetyl-CoA and histone H3 peptides, and it can bind simultaneously to the free enzyme and the enzyme-substrate complex. By blocking the acetylation of histones, it modulates the epigenetic regulation of gene expression.
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| ln Vitro |
EML 425 (EML425, Compound 7h) is a strong, reversible, and specific inhibitor of CBP/p300. It exhibits good cell permeability and is non-competitive with acetyl-CoA and histone H3 peptides. EML 425 exhibits minimal activity against the general control non-derepressor 5 (GCN5) and p300/CBP-associated factor (PCAF) enzymes, but it effectively suppresses p300 and CBP (IC50 values 2.9 and 1.1 μM, respectively). EML 425 substantially and time-dependently acetylates lysine H4K5 and H3K9 in U937 cells. It was demonstrated that EML 425 is a reversible inhibitor with uneven affinity constants that can bind both free enzyme and enzyme-substrate complexes. It is also non-competitive with acetyl-CoA and histone H3 peptides. According to the best-scoring docking position, the binding site for EML 425 is an alternate pocket that is situated close to the acetylation site and close to the substrate's lysine binding groove [1].
In vitro, EML 425 potently inhibits the histone acetyltransferase activity of CBP and p300 with IC₅₀ values of 2.9 and 1.1 µM, respectively. It is a reversible and non-competitive inhibitor that is effective against both acetyl-CoA and histone H3 peptides, and it can bind simultaneously to the free enzyme and the enzyme-substrate complex. The compound has demonstrated the ability to prevent glucose-induced cataract formation in isolated rat lenses when used at a concentration of 200 µM. |
| ln Vivo |
In vivo activity for EML 425 has not been extensively documented in the available literature. Its role as a tool compound suggests it could be used in animal models to study the effects of CBP/p300 inhibition on gene expression and disease progression. Its good cell permeability and potency make it a suitable candidate for further in vivo investigation, particularly for studying human leukemia and other diseases where epigenetic regulation plays a critical role.
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| Enzyme Assay |
Non-cellular assays for EML 425 are based on its inhibition of the histone acetyltransferase (HAT) activity of CBP and p300. These assays typically use purified recombinant enzymes and a radiolabeled or biotinylated acetyl-CoA donor. The enzyme is incubated with a peptide substrate (e.g., a histone H3 peptide) and varying concentrations of EML 425. The incorporation of the acetyl group into the substrate is measured, often using a scintillation proximity assay (SPA) or an ELISA-based format. The IC₅₀ values are determined from the resulting dose-response curves.
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| Cell Assay |
In vitro cellular assays for EML 425 involve treating cells, such as human leukemia cell lines, with the compound to assess its effects on histone acetylation and gene expression. Cells are exposed to varying concentrations of EML 425 for a defined period. Histone acetylation levels, specifically at lysine residues targeted by CBP/p300, are then measured by Western blotting using acetylation-specific antibodies. Changes in the expression of genes regulated by CBP/p300 can be quantified by qPCR or RNA-seq to understand the downstream consequences of inhibiting these histone acetyltransferases.
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| Animal Protocol |
In vivo animal experiments for EML 425 are not extensively documented in the available literature. Given its mechanism as an epigenetic modulator, potential studies would involve administering EML 425 to animal models of disease, such as leukemia xenografts. Endpoints would include tumor growth inhibition, assessment of histone acetylation and gene expression changes in tumor tissue, and evaluation of the compound's pharmacokinetic properties and tolerability.
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| ADME/Pharmacokinetics |
EML 425 has a molecular weight of 440.49 and a molecular formula of C₂₇H₂₄N₂O₄. It is a solid powder with a purity of 99.49%. The compound is soluble in DMSO (88 mg/mL) and ethanol (2 mg/mL), but insoluble in water. For storage, the powder should be kept at -20°C for up to 3 years or at 4°C for up to 2 years; stock solutions in solvent can be stored at -80°C for 6 months or at -20°C for 1 month.
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| Toxicity/Toxicokinetics |
EML 425 is a research compound for laboratory use only and is not intended for human therapeutic or diagnostic use. In preclinical studies, it has been generally well-tolerated. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation. Appropriate personal protective equipment should be used. As a histone acetyltransferase inhibitor, it may have effects on gene expression in normal cells.
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| References | |
| Additional Infomation |
EML 425 (CAS 1675821-32-5) is a potent, selective, reversible, and non-competitive inhibitor of the histone acetyltransferases CBP and p300, with IC₅₀ values of 2.9 and 1.1 µM, respectively. It is a diazinane derivative and a valuable tool compound for studying the role of CBP/p300 in epigenetic regulation, particularly in the context of human leukemia cells. It is available from various commercial suppliers for research applications.
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| Molecular Formula |
C27H24N2O4
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|---|---|
| Molecular Weight |
440.5
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| Exact Mass |
440.173
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| CAS # |
1675821-32-5
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| PubChem CID |
91826273
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
622.8±65.0 °C at 760 mmHg
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| Flash Point |
330.5±34.3 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.683
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| LogP |
4.71
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
710
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=CC(=C1C=C2C(=O)N(C(=O)N(C2=O)CC3=CC=CC=C3)CC4=CC=CC=C4)C)O
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| InChi Key |
LUGQBJDYUPNAQQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H24N2O4/c1-18-13-22(30)14-19(2)23(18)15-24-25(31)28(16-20-9-5-3-6-10-20)27(33)29(26(24)32)17-21-11-7-4-8-12-21/h3-15,30H,16-17H2,1-2H3
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| Chemical Name |
1,3-dibenzyl-5-[(4-hydroxy-2,6-dimethylphenyl)methylidene]-1,3-diazinane-2,4,6-trione
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| Synonyms |
EML425; EML-425; EML 425
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 250 mg/mL (~567.55 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2701 mL | 11.3507 mL | 22.7015 mL | |
| 5 mM | 0.4540 mL | 2.2701 mL | 4.5403 mL | |
| 10 mM | 0.2270 mL | 1.1351 mL | 2.2701 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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