| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
The primary target of TMI-1 is ADAM17 (TACE) and other matrix metalloproteinases (MMPs). It acts as a potent inhibitor, binding to these enzymes and inhibiting their activity. TMI-1 has an IC50 of 8.4 nM for ADAM17 and IC50s of 6.6, 4.7, 26, 12, 3, and 26 nM for MMP-1, -2, -7, -9, -13, and -14, respectively.
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| ln Vitro |
In vitro, TMI-1 inhibits ADAM17 with an IC50 of 8.4 nM and inhibits various MMPs. It effectively inhibits LPS-induced TNF-α secretion in human primary monocytes and human whole blood. TMI-1 inhibits cancer cell proliferation and induces apoptosis through a caspase-dependent pathway.
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| ln Vivo |
In vivo, TMI-1 protects against paclitaxel-induced neurotoxicity by reversing TRPV1 upregulation and lowering the levels of inflammatory factors (TNF-α, IL-1β, IL-6) in nerve cells. However, specific in vivo efficacy data from animal models are limited in the available literature.
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| Enzyme Assay |
In vitro enzyme or receptor binding assays for TMI-1 involve measuring its inhibition of ADAM17 and MMP activity. The assay uses a purified recombinant enzyme and a fluorogenic peptide substrate. The cleavage of the substrate releases a fluorescent product. The compound is incubated with the enzyme and substrate at varying concentrations to determine the IC50.
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| Cell Assay |
In vitro cell-based assays for TMI-1 are performed using human primary monocytes and whole blood. Cells are treated with the compound and stimulated with LPS. The production of TNF-α is measured by ELISA. Cancer cell lines are treated with the compound, and cell proliferation and apoptosis are assessed.
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| Animal Protocol |
In vivo animal experiments for TMI-1 are conducted using models of paclitaxel-induced neurotoxicity. The compound is administered, and its effects on TRPV1 expression and inflammatory factors in nerve cells are assessed. However, specific detailed protocols are limited.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TMI-1 indicate that it has a molecular weight of 398.50 and a molecular formula of C17H22N2O5S2. The CAS number is 287403-39-8. It is soluble in DMSO at 39.85 mg/mL. Powder is stable when stored at -20°C for 3 years or at 4°C for 2 years.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for TMI-1 are characteristic of a research compound. As an ADAM17 and MMP inhibitor, its safety profile is an important consideration. The compound is generally well-tolerated at effective doses in preclinical models. However, its long-term safety profile requires further evaluation.
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| References |
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| Additional Infomation |
Other information: TMI-1 is a potent inhibitor of ADAM17 and MMPs. It is also known as WAY-171318. The compound inhibits LPS-induced TNF-α secretion and protects against paclitaxel-induced neurotoxicity. Its CAS number is 287403-39-8.
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| Molecular Formula |
C17H22N2O5S2
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|---|---|
| Molecular Weight |
398.496982097626
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| Exact Mass |
398.097
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| CAS # |
287403-39-8
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| Related CAS # |
TMI-1; 287403-39-8
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| PubChem CID |
5288615
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.590
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| LogP |
2.56
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
666
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC#CCOC1=CC=C(C=C1)S(=O)(=O)N2CCSC([C@@H]2C(=O)NO)(C)C
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| InChi Key |
CVZIHNYAZLXRRS-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C17H22N2O5S2/c1-4-5-11-24-13-6-8-14(9-7-13)26(22,23)19-10-12-25-17(2,3)15(19)16(20)18-21/h6-9,15,21H,10-12H2,1-3H3,(H,18,20)/t15-/m0/s1
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| Chemical Name |
(3S)-4-(4-but-2-ynoxyphenyl)sulfonyl-N-hydroxy-2,2-dimethylthiomorpholine-3-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 : ≥ 100 mg/mL (~250.94 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 | 2.5094 mL | 12.5471 mL | 25.0941 mL | |
| 5 mM | 0.5019 mL | 2.5094 mL | 5.0188 mL | |
| 10 mM | 0.2509 mL | 1.2547 mL | 2.5094 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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