| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
MAK-683 targets EED by selectively binding to the domain that interacts with trimethylated lysine 27 on histone 3 (H3K27me3). This binding induces a conformational change in the EED H3K27me3-binding pocket, preventing EED interaction with the histone methyltransferase enhancer of zeste homolog 2 (EZH2). Allosteric blockade of the EED-H3K27me3 interaction suppresses PRC2 activity and reduces H3K27me3 levels.
|
|---|---|
| ln Vitro |
After 14 days of therapy, MAK683 has an IC50 of 30 nM against B-cell lymphoma cells KARPAS422 that exhibits anti-proliferative action [1].
In vitro, MAK-683 shows potent inhibition of EED in biochemical assays with IC₅₀ values of 59 nM in EED Alphascreen binding, 89 nM in LC-MS, and 26 nM in ELISA assays. In B-cell lymphoma KARPAS422 cells, MAK-683 exhibits anti-proliferative activity with an IC₅₀ of 30 nM after 14 days of treatment. The compound derepresses tumor-suppressor genes by reducing H3K27me3 levels. |
| ln Vivo |
In vivo, MAK-683 demonstrates antitumor activity in preclinical models by allosterically inhibiting PRC2. Upon administration, the compound selectively binds to EED, prevents its interaction with EZH2, and suppresses PRC2 activity. This leads to reduced H3K27me3 levels and derepression of tumor-suppressor genes, resulting in antineoplastic effects. Detailed in vivo efficacy data in specific animal models is limited in publicly available sources.
|
| Enzyme Assay |
The EED Alphascreen binding assay is a non-cellular assay used to evaluate MAK-683's affinity for EED. Recombinant EED protein and biotinylated H3K27me3 peptide are incubated with varying concentrations of the compound. Alpha donor and acceptor beads are added, and the signal is measured. IC₅₀ values are calculated from dose-response curves. Additional assays include LC-MS and ELISA-based binding measurements.
|
| Cell Assay |
In vitro cellular activity is evaluated using B-cell lymphoma KARPAS422 cells. Cells are treated with MAK-683 at various concentrations for 14 days. Cell viability and proliferation are measured using standard assays such as CellTiter-Glo or MTT. Anti-proliferative activity is reported as IC₅₀ values. H3K27me3 levels in treated cells can be measured by Western blot to confirm target engagement and PRC2 inhibition.
|
| Animal Protocol |
In vivo animal studies typically involve tumor xenograft models. Immunocompromised mice bearing KARPAS422 or other PRC2-dependent tumor xenografts are treated with MAK-683 via oral administration or other routes. Tumor volume is measured over time to assess antitumor efficacy. H3K27me3 levels in tumor tissues are analyzed to confirm pharmacodynamic effects. Survival and body weight are also monitored.
|
| ADME/Pharmacokinetics |
MAK-683 is soluble in DMSO. Pharmacokinetic properties include oral bioavailability and tissue distribution consistent with small molecule inhibitors. The compound is administered in vivo using formulations such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline. Storage conditions: powder at -20°C for 1 year; in solvent at -80°C for 1 year.
|
| Toxicity/Toxicokinetics |
Toxicological data for MAK-683 is limited in publicly available sources. As a potent inhibitor of EED/PRC2, it is expected to have on-target effects related to epigenetic regulation. Standard preclinical toxicology studies would be required for therapeutic development. The compound is for research use only and should be handled with appropriate safety precautions.
|
| References | |
| Additional Infomation |
MAK683, an EED inhibitor, is an inhibitor of embryonic ectodermal developmental protein (EED) and a polycomb inhibitory complex 2 (PRC2) allosteric inhibitor with potential antitumor activity. Upon administration, MAK683 selectively binds to a domain in EED that interacts with the histone H3 27-lysine trimethylation (H3K27me3), leading to a conformational change in the EED's H3K27me3 binding pocket, thereby preventing the interaction between EED and histone methyltransferase enhancer Zeste homolog 2 (EZH2). Disruption of the EED-EZH2 protein-protein interaction (PPI) results in loss of H3K27me3-stimulated PRC2 activity and prevention of H3K27 trimethylation. Decreased histone methylation alters gene expression patterns associated with cancer pathways and leads to reduced proliferation of EZH2-mutant and PRC2-dependent cancer cells. PRC2 is a histone H3 lysine 27-methyltransferase composed of EZH2, EED, and repressor 12 (SUZ12). It is a multi-protein complex that plays a crucial role in gene regulation, particularly during embryonic development. EZH2 is the catalytic subunit of PRC2 and is overexpressed or mutated in various cancer cells. EED is essential for the histone methyltransferase activity of PRC2 because it directly binds to H3K27me3.
MAK-683 (also known as EZM0414) is a synthetic small molecule allosteric inhibitor of EED and PRC2. It is being investigated for potential antineoplastic activity. The compound is referenced in patent US20160176882 A1. By blocking the EED-H3K27me3 interaction, MAK-683 suppresses PRC2 activity and reduces H3K27me3 levels, leading to derepression of tumor-suppressor genes. This product is for research purposes only. |
| Molecular Formula |
C20H17FN6O
|
|---|---|
| Molecular Weight |
376.386986494064
|
| Exact Mass |
376.144
|
| CAS # |
1951408-58-4
|
| Related CAS # |
MAK683 hydrochloride;2170606-94-5
|
| PubChem CID |
121412508
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.4
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
28
|
| Complexity |
541
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C=CC2=C(C=1CNC1=NC=C(C3=CC=CN=C3C)C3=NN=CN13)CCO2
|
| InChi Key |
XLIBABIFOBYHSV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H17FN6O/c1-12-13(3-2-7-22-12)16-10-24-20(27-11-25-26-19(16)27)23-9-15-14-6-8-28-18(14)5-4-17(15)21/h2-5,7,10-11H,6,8-9H2,1H3,(H,23,24)
|
| Chemical Name |
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine
|
| Synonyms |
MAK683 MAK 683 MAK-683 EED inhibitor-1 EED inhibitor 1 EED inhibitor1
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~40 mg/mL (~106.27 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.17 mg/mL (5.77 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 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. Solubility in Formulation 2: ≥ 2.17 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6568 mL | 13.2841 mL | 26.5682 mL | |
| 5 mM | 0.5314 mL | 2.6568 mL | 5.3136 mL | |
| 10 mM | 0.2657 mL | 1.3284 mL | 2.6568 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
