| 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 |
2.40 μM (Microtubule/Tubulin)[1]
NEDDylation is a protein post-translational modification that covalently tags the ubiquitin-like protein NEDD8 to target proteins. Tubulin/NEDDylation-IN-1 targets two critical biological pathways: tubulin dynamics, essential for mitosis and cellular structure, and neddylation, which regulates protein function through modification of cullin-RING ligase complexes. It inhibits NEDDylation and microtubulin in an ATP-dependent manner. |
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| ln Vitro |
In vitro studies demonstrate that Tubulin/NEDDylation-IN-1 is a dual inhibitor of microtubule/tubulin polymerization and NEDDylation with an IC50 of 2.40 μM for microtubule inhibition. It forms hydrogen bonds with residues of tubulin and E1 NEDD8 activating enzyme (NAE) through methoxy and dithiocarbamate groups. The compound exhibits strong antiproliferative activity. Detailed cellular activity data against specific cancer cell lines are not extensively documented.
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| ln Vivo |
In vivo activity of Tubulin/NEDDylation-IN-1 is inferred from its dual mechanism of action targeting tubulin and NEDDylation pathways. By inhibiting both microtubule polymerization and NEDDylation, the compound is expected to have potent antitumor activity. Detailed in vivo efficacy data from animal models, including tumor growth inhibition studies, are not extensively documented in the available literature.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for Tubulin/NEDDylation-IN-1 involves measuring its inhibitory activity against tubulin polymerization and NEDD8-activating enzyme (NAE). For tubulin polymerization assays, purified tubulin is incubated with the compound, and polymerization is monitored spectrophotometrically. For NAE inhibition, purified NAE enzyme is incubated with the compound, and NEDD8 transfer to substrate is measured. IC50 values are determined by plotting percentage inhibition against compound concentration.
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| Cell Assay |
In vitro cell-based assays for Tubulin/NEDDylation-IN-1 are conducted using cancer cell lines to evaluate its antiproliferative effects. Cells are treated with the compound at various concentrations, and cell viability is measured using MTT or CCK-8 assays. The effect on microtubule dynamics is assessed by immunofluorescence microscopy of tubulin staining. NEDDylation levels are measured by Western blot using anti-NEDD8 antibodies. Apoptosis induction is evaluated by measuring caspase activation.
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| Animal Protocol |
In vivo animal studies for Tubulin/NEDDylation-IN-1 would typically be conducted using xenograft mouse models. Tumor-bearing mice would be administered the compound via appropriate routes, and tumor growth inhibition would be monitored. Pharmacokinetic parameters would be determined from plasma samples. Tolerability would be assessed by monitoring body weight changes and clinical signs. However, detailed protocols and efficacy data are not available from the search results.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Tubulin/NEDDylation-IN-1 are not extensively documented in the available literature. As a dual inhibitor with a first-in-class mechanism, its pharmacokinetic profile would be important for determining its suitability for in vivo studies. The compound's formulation, solubility, and stability would need to be optimized for in vivo administration. Detailed pharmacokinetic data are not available from the search results.
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| Toxicity/Toxicokinetics |
Toxicity information for Tubulin/NEDDylation-IN-1 is limited. Standard safety precautions for handling research chemicals should be followed. The compound is designated for research use only and is not for human therapeutic applications. As a dual inhibitor targeting essential cellular pathways, it may have significant toxicity that should be evaluated in appropriate studies. No detailed toxicity data are available from the search results.
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| References | |
| Additional Infomation |
Tubulin/NEDDylation-IN-1 (compound C11) is a first-in-class, small-molecule dual inhibitor that simultaneously targets microtubule/tubulin polymerization and the NEDD8-activating enzyme (NAE)-dependent NEDDylation pathway. It inhibits microtubule polymerization with an IC50 of 2.40 μM. It forms hydrogen bonds with residues of tubulin and NAE. It exhibits strong antiproliferative activity.
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| Molecular Formula |
C25H32N2O5S2
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|---|---|
| Molecular Weight |
504.66
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| Appearance |
Light yellow to 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 |
| 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 :~100 mg/mL (~198.15 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication.
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 and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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: 2.5 mg/mL (4.95 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. 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 and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. 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. View More
Solubility in Formulation 3: 2.5 mg/mL (4.95 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9815 mL | 9.9077 mL | 19.8153 mL | |
| 5 mM | 0.3963 mL | 1.9815 mL | 3.9631 mL | |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9815 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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