| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
The compound targets MNK1 (MAP kinase-interacting kinase 1) and MNK2 (MAP kinase-interacting kinase 2). MNKs are the only kinases known to phosphorylate eIF4E at Ser209, a modification that promotes the translation of oncogenic mRNAs (e.g., c-Myc, cyclin D1, Mcl-1, VEGF). By inhibiting MNK1/2, MNK1/2-IN-5 prevents eIF4E phosphorylation, thereby suppressing the translation of key cancer-promoting proteins without affecting global protein synthesis.
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| ln Vitro |
Specific IC50 values for MNK1/2-IN-5 against MNK1 and MNK2 are not detailed in the literature, but the compound is described as a potent and selective MNK1/2 inhibitor. It demonstrates anticancer activity in cellular models, suppressing eIF4E phosphorylation and reducing the expression of oncogenic proteins. It can be used to study solid tumors, including cancers of the colon, lung, and breast, as well as hematological malignancies, offering a distinct approach to cancer therapy through translation inhibition.
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| ln Vivo |
Specific in vivo data for MNK1/2-IN-5 are not detailed. As a potent MNK1/2 inhibitor, it would be expected to show efficacy in mouse xenograft models of solid tumors and hematological malignancies. A typical protocol would involve oral or intraperitoneal administration (e.g., 10-50 mg/kg daily) to assess tumor growth inhibition, with pharmacodynamic endpoints including measurement of p-eIF4E levels in tumor tissue by Western blot.
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| Enzyme Assay |
The activity of MNK1/2-IN-5 is typically assessed using a radiometric or luminescent kinase assay. Recombinant human MNK1 or MNK2 kinase is incubated with a peptide substrate (e.g., eIF4E-derived peptide) and ATP (at Km concentration) in the presence of varying concentrations of the inhibitor in reaction buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT). After incubation at 30degC for 30-60 minutes, the reaction is stopped, and the amount of ADP produced is measured using an ADP-Glo™ luminescence assay to calculate IC50 values.
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| Cell Assay |
A cellular assay is performed in cancer cell lines such as HCT116 (colon cancer), A549 (lung cancer), or MCF-7 (breast cancer). Cells are treated with varying concentrations of MNK1/2-IN-5 (0.1-100 uM) for 2-24 hours. After treatment, cells are lysed, and the levels of phospho-eIF4E (Ser209), total eIF4E, and downstream targets (e.g., c-Myc, Mcl-1) are analyzed by Western blot. Cell viability is assessed after 48-72 hours of treatment using MTT or CellTiter-Glo assays to determine the anti-proliferative activity.
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| Animal Protocol |
In vivo efficacy is evaluated in a mouse xenograft model of human cancer. Female nude mice are injected subcutaneously with cancer cells (e.g., HCT116 colon cancer cells). When tumors reach ~150-200 mm3, mice are randomized into treatment groups. MNK1/2-IN-5 is administered via oral gavage or intraperitoneal injection at doses of 10-50 mg/kg daily for 2-3 weeks. Tumor volume is measured by calipers twice weekly. On study termination, tumors are harvested for analysis of p-eIF4E levels, total eIF4E, and expression of oncogenic proteins by Western blot and immunohistochemistry.
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| ADME/Pharmacokinetics |
Specific PK parameters for MNK1/2-IN-5 are not detailed. As a small molecule with molecular weight 308.33 g/mol and favorable physicochemical properties (LogP not specified, but moderate lipophilicity is expected), it is likely to have good oral bioavailability. The compound is soluble in DMSO (7.14 mg/mL), and in vivo formulations can be prepared using vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline.
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| Toxicity/Toxicokinetics |
Specific toxicological data for MNK1/2-IN-5 are not detailed. As a selective inhibitor of MNK1/2, which are not essential for normal cell viability, the compound may have a favorable safety profile. However, eIF4E phosphorylation is important for stress responses and certain physiological processes. Standard toxicological endpoints in animal studies would include body weight monitoring, hematological parameters, and histopathological examination of major organs.
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| References | |
| Additional Infomation |
MNK1/2-IN-5 is a research-grade chemical tool for studying the MNK-eIF4E signaling axis in cancer biology. The MNK-eIF4E pathway is a promising therapeutic target because eIF4E is overexpressed and hyperphosphorylated in many cancers, and its inhibition selectively suppresses the translation of oncogenic mRNAs without affecting global translation. As of the latest updates, this compound has not been approved for clinical use and is exclusively available for research.
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| Molecular Formula |
C17H16N4O2
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|---|---|
| Molecular Weight |
308.33
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| Exact Mass |
308.127
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| CAS # |
1426928-20-2
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| PubChem CID |
71468412
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
410
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1C2=CC=CC=C2C=C1C1=CN=C2C=CC(=NN12)O[C@H](C)CN
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| InChi Key |
CMDIADSAZCFCCT-LLVKDONJSA-N
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| InChi Code |
InChI=1S/C17H16N4O2/c1-11(9-18)22-17-7-6-16-19-10-13(21(16)20-17)15-8-12-4-2-3-5-14(12)23-15/h2-8,10-11H,9,18H2,1H3/t11-/m1/s1
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| Chemical Name |
(2R)-2-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxypropan-1-amine
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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 : ~7.14 mg/mL (~23.16 mM)
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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 | 3.2433 mL | 16.2164 mL | 32.4328 mL | |
| 5 mM | 0.6487 mL | 3.2433 mL | 6.4866 mL | |
| 10 mM | 0.3243 mL | 1.6216 mL | 3.2433 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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