| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
DS-12881479 targets MNK1 (MAP kinase-interacting serine/threonine protein kinase 1), a kinase that phosphorylates eukaryotic translation initiation factor 4E (eIF4E). MNK1 is activated downstream of the MAPK pathways (ERK and p38) and plays a role in regulating protein translation, cell proliferation, and survival. By inhibiting MNK1, DS-12881479 reduces eIF4E phosphorylation, which may affect the translation of oncogenic mRNAs and inhibit cancer cell growth. The compound also inhibits FLT3 and DYRK1A at higher concentrations.
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| ln Vitro |
In vitro, DS-12881479 inhibits MNK1 activity with an IC50 of 21 nM. It shows selectivity for MNK1 over 46 other kinases, though it does inhibit FLT3 and DYRK1A at 5 µM. The compound's potent and selective MNK1 inhibition makes it a valuable tool for studying the role of MNK1 in cancer cell proliferation, survival, and drug resistance. Its activity against the inactive and active forms of MNK1 has IC50 values of 21 and 416 nM, respectively.
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| ln Vivo |
In vivo efficacy data for DS-12881479 have not been detailed in the available literature. Based on its potent in vitro MNK1 inhibition and potential for cancer research, the compound may have applications in in vivo cancer models. However, specific studies on tumor growth inhibition, pharmacokinetics, and tolerability in animal models would be required to assess its therapeutic potential. The compound is currently a research tool for studying MNK1 biology.
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| Enzyme Assay |
For in vitro kinase assays, recombinant MNK1 protein is incubated with a peptide substrate (such as eIF4E-derived peptide) and ATP in kinase assay buffer. The test compound is added at various concentrations (typically 0.001-100 µM). Kinase activity can be measured using radioactive ATP (³³P-ATP) incorporation, followed by filter binding and scintillation counting, or using non-radioactive methods such as luminescent ADP detection assays (e.g., ADP-Glo). IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
For cell-based assays, cancer cell lines are treated with DS-12881479 at concentrations ranging from 0.01-10 µM for various time points. MNK1 activity is assessed by measuring the phosphorylation status of eIF4E (Ser209) by Western blotting. Cell viability and proliferation are measured using MTT, CCK-8, or CellTiter-Glo assays. Apoptosis can be assessed by Annexin V staining or caspase activity assays. The compound's effects on protein synthesis can be evaluated using puromycin incorporation assays or polysome profiling.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice would be implanted with cancer cell lines that are sensitive to MNK1 inhibition. When tumors reach a predetermined size, mice would be randomized to receive DS-12881479 via oral or intraperitoneal administration at doses determined from pharmacokinetic studies. Tumor volumes would be measured twice weekly. At study endpoint, tumors would be collected for Western blot analysis of phospho-eIF4E to confirm target inhibition. However, specific in vivo protocols have not been reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of DS-12881479 have not been fully characterized in the available literature. The compound has a molecular weight of 301.41 g/mol, suggesting potential for drug-like properties. Standard PK studies including solubility, permeability, half-life, oral bioavailability, and tissue distribution would be required to support in vivo studies. The compound is typically stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Toxicological data for DS-12881479 have not been reported. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References | |
| Additional Infomation |
DS-12881479 is a potent and selective MNK1 inhibitor with an IC50 of 21 nM. It shows selectivity for MNK1 over 46 other kinases but inhibits FLT3 and DYRK1A at 5 µM. The compound can be used in cancer research. DS-12881479 inhibits MNK1-mediated eIF4E phosphorylation, which regulates protein translation and cancer cell proliferation. It is a research tool and is not approved for clinical use.
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| Molecular Formula |
C16H19N3OS
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|---|---|
| Molecular Weight |
301.40656208992
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| Exact Mass |
301.124
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| CAS # |
2373065-59-7
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| PubChem CID |
131953480
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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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 |
3
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| Heavy Atom Count |
21
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| Complexity |
351
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C)CCC(C(NC2=NC=C(C3=CC=CC=C3)S2)=O)CC1
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| InChi Key |
BTZKRRFKIKIADV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19N3OS/c1-19-9-7-13(8-10-19)15(20)18-16-17-11-14(21-16)12-5-3-2-4-6-12/h2-6,11,13H,7-10H2,1H3,(H,17,18,20)
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| Chemical Name |
1-methyl-N-(5-phenyl-1,3-thiazol-2-yl)piperidine-4-carboxamide
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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 (~829.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.90 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 20.8 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 | 3.3177 mL | 16.5887 mL | 33.1774 mL | |
| 5 mM | 0.6635 mL | 3.3177 mL | 6.6355 mL | |
| 10 mM | 0.3318 mL | 1.6589 mL | 3.3177 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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