| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
Methuosis inducer 1 targets PIKfyve and tubulin. PIKfyve is a lipid kinase that regulates endosomal membrane dynamics, and its inhibition leads to the formation of vacuoles characteristic of methuosis. Tubulin is a protein involved in microtubule formation, essential for cell division and intracellular transport. By dual-targeting PIKfyve and tubulin, the compound induces methuotic cell death and exhibits anti-tumor activity.
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| ln Vitro |
With IC50 values of 0.326±0.026 μM, 1.370±0.061 μM, 1.662±0.128 μM, 1.892±0.092 μM, 1.571±0.066 μM, A375, SK-MEL-28, SK-MEL-30, A549, MDA-MB-231, MDA-2.268±0.100 μM, 2.611±0.739 μM, 1.008±0.042 μM, 1.566±0.015 μM, and 1.197±0.344 μM, respectively, demonstrated broad spectrum cytotoxicity against a panel of human cancer cell lines. They are HepG2 cells, BGC823, HCT116, MCF-7, and MB-435S [1].
In vitro, Methuosis inducer 1 shows a broad spectrum of cytotoxicity against a panel of human cancer cell lines with IC₅0 values of 0.326+/-0.026 microM for A375 cells. It exhibits IC₅0 values of 1.370+/-0.061 microM (SK-MEL-28), 1.662+/-0.128 microM (SK-MEL-30), 1.892+/-0.092 microM (A549), 1.571+/-0.066 microM (MDA-MB-231), and others. The compound induces methuosis, a unique form of non-apoptotic cell death. |
| ln Vivo |
In vivo, Methuosis inducer 1 exhibits substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects. This makes the compound the first example of a methuosis inducer with potent in vivo efficacy. These results suggest that methuosis inducers have potential as novel cancer therapeutics.
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| Enzyme Assay |
For in vitro binding assays, Methuosis inducer 1 can be evaluated using kinase activity assays to measure PIKfyve inhibition. The compound is incubated with recombinant PIKfyve and ATP at various concentrations. Kinase activity is quantified by measuring phosphorylation of substrates. Binding affinity (Kd=10.4 nM) can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Tubulin polymerization assays can be used to assess effects on microtubule dynamics.
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| Cell Assay |
For in vitro cellular experiments, Methuosis inducer 1 is tested in cancer cell lines such as A375, MDA-MB-231, and MCF-7. Cells are cultured in appropriate media and treated with various concentrations of the compound. Cell viability is assessed using MTT or CellTiter-Glo assays. Vacuole formation, characteristic of methuosis, is visualized by microscopy. Apoptosis and other cell death pathways are evaluated to confirm the methuosis mechanism.
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| Animal Protocol |
For in vivo animal experiments, Methuosis inducer 1 can be administered to tumor-bearing mice via intraperitoneal injection. Xenograft models using MDA-MB-231 cells in immunodeficient mice are commonly used. Typical doses may range from 1 to 50 mg/kg. Tumor volume is measured regularly, and tumor growth inhibition is calculated. Body weight and overall health are monitored as indicators of tolerability.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Methuosis inducer 1 are not extensively detailed in the public literature. As a small molecule with a molecular weight of 487.48, it may have reasonable bioavailability and tissue distribution. The compound is soluble in DMSO at 120 mg/mL. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies.
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| Toxicity/Toxicokinetics |
Toxicological data for Methuosis inducer 1 indicate that it is well-tolerated in vivo at efficacious doses. In xenograft mouse models, the compound exhibits substantial pharmacological efficacy without apparent side effects. Standard toxicological assessments would include acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity evaluations. As with all research chemicals, appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
Methuosis inducer 1 is a research compound used to study methuosis and develop novel cancer therapeutics. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is the first example of a methuosis inducer with potent in vivo efficacy.
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| Molecular Formula |
C27H20F3N5O
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|---|---|
| Molecular Weight |
487.47581577301
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| Exact Mass |
487.161
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| CAS # |
2240205-30-3
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| PubChem CID |
138319688
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
751
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)C(F)(F)F)NC3=CC(=NC4=C3C=CN4)C5=CN=CC=C5
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| InChi Key |
MNEWQRRQMLENPL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H20F3N5O/c1-16-7-8-20(33-26(36)17-4-2-6-19(12-17)27(28,29)30)13-22(16)34-24-14-23(18-5-3-10-31-15-18)35-25-21(24)9-11-32-25/h2-15H,1H3,(H,33,36)(H2,32,34,35)
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| Chemical Name |
N-[4-methyl-3-[(6-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)amino]phenyl]-3-(trifluoromethyl)benzamide
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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 : ~25 mg/mL (~51.28 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.13 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (4.45 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 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0514 mL | 10.2568 mL | 20.5137 mL | |
| 5 mM | 0.4103 mL | 2.0514 mL | 4.1027 mL | |
| 10 mM | 0.2051 mL | 1.0257 mL | 2.0514 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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