| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MAK683-CH2CH2COOH targets EED, a key component of the PRC2 complex. MAK683 (parent compound) binds EED with IC50 values of 59 nM (Alphascreen), 26 nM (ELISA), and 89 nM (LC-MS assay). The CH2CH2COOH extension enables conjugation to E3 ubiquitin ligase ligands via amide bond formation.
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| ln Vitro |
After 14 days of treatment, MAK683-CH2CH2COOH inhibits Karpas422 cells with a GI50 of 14 nM [1].
Not available. MAK683 is a potent EED inhibitor. The functionalized derivative MAK683-CH2CH2COOH retains EED-binding activity via the MAK683 pharmacophore, while the carboxyl group serves as an attachment point. The compound alone has no intrinsic activity beyond EED binding; activity is realized when incorporated into PROTACs. |
| ln Vivo |
Not available. MAK683-CH2CH2COOH has been used to design EED-targeted PROTACs (EED degrader-1 and PROTAC EED degrader-2) by linking this ligand with a VHL E3 ubiquitin ligase ligand. In cells, these PROTACs induce EED degradation, leading to reduced H3K27me3 levels and anti-proliferative effects in PRC2-dependent cancer models.
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| Enzyme Assay |
Standard EED binding assays involve incubating MAK683-CH2CH2COOH (1 pM to 10 uM) with recombinant EED protein in Alphascreen buffer (25 mM HEPES, pH 7.5, 0.1% BSA, 0.05% Tween-20) at room temperature for 1 hour, followed by addition of donor and acceptor beads. Luminescence is measured after 2 hours. For ELISA, biotinylated EED is captured on streptavidin-coated plates, and binding is detected with labeled secondary antibody.
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| Cell Assay |
Not available. For PROTAC activity assays, typical protocols involve treating PRC2-dependent cancer cells (e.g., KARPAS-422, Pfeiffer) with EED PROTACs (0.1-1000 nM) for 4-24 hours, followed by Western blotting to quantify EED and H3K27me3 levels. Cell viability is assessed by MTT or CellTiter-Glo after 72-120 hours of treatment.
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| Animal Protocol |
Not available. For in vivo efficacy of EED PROTACs, standard protocols involve intravenous or intraperitoneal administration (typically 10-100 mg/kg) in tumor-bearing xenograft mouse models, with assessment of EED degradation in tumor tissue by Western blot at 4-24 hours post-dose, and tumor growth inhibition monitored over 2-4 weeks.
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| ADME/Pharmacokinetics |
The CH2CH2COOH extension increases polarity and improves aqueous solubility compared to unmodified MAK683. The carboxyl group enables amide coupling to amine-functionalized E3 ligase ligands using standard HATU or EDC/NHS chemistry. The TFA salt form in related compounds (not this hydrochloride) enhances solubility.
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| Toxicity/Toxicokinetics |
MAK683 itself has a manageable safety profile in preclinical studies. As a PROTAC building block, MAK683-CH2CH2COOH hydrochloride is not intended for in vivo use as a free compound. Specific toxicological data are not reported. Standard laboratory safety precautions apply.
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| References | |
| Additional Infomation |
MAK683-CH2CH2COOH hydrochloride is a research-grade PROTAC building block for EED-targeted protein degradation. MAK683 is an investigational EED inhibitor that has been evaluated in preclinical studies for PRC2-dependent cancers. This functionalized derivative is for laboratory research in PROTAC development and epigenetic cancer therapy, not for clinical use.
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| Molecular Formula |
C23H22CLFN6O3
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|---|---|
| Molecular Weight |
484.91
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| Related CAS # |
MAK683-CH2CH2COOH;2639882-68-9
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| Appearance |
White to light yellow solid powder
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0622 mL | 10.3112 mL | 20.6224 mL | |
| 5 mM | 0.4124 mL | 2.0622 mL | 4.1245 mL | |
| 10 mM | 0.2062 mL | 1.0311 mL | 2.0622 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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