| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
The primary targets of Apratastat are TACE (also known as ADAM17) and matrix metalloproteinases (MMPs). TACE is responsible for the proteolytic release of membrane-bound proteins, most notably the pro-inflammatory cytokine TNF-α. By inhibiting TACE and MMPs, Apratastat reduces the release of TNF-α and other inflammatory mediators, thereby modulating inflammatory and tissue-destructive processes. The compound acts as a reversible, non-selective inhibitor of these enzymes.
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| ln Vitro |
Apratastat demonstrates potent in vitro inhibition of TACE and MMPs. It potently inhibits the release of TNF-α in vitro with an IC50 of 144 ng/mL. The compound's dual inhibition of TACE and MMPs makes it effective in reducing inflammation and tissue damage in vitro. However, detailed IC50 values for specific MMP targets are not extensively reported in the available literature.
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| ln Vivo |
Apratastat demonstrates in vivo efficacy in inhibiting TNF-α release, with an ex vivo IC50 of 81.7 ng/mL. The compound is orally active, indicating good oral bioavailability. It has been investigated for potential use in conditions like rheumatoid arthritis, where excessive inflammation and tissue damage are key issues. Apratastat also has the potential to overcome radiotherapy resistance in non-small cell lung cancer.
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| Enzyme Assay |
In vitro enzyme assays for Apratastat typically involve measuring its inhibition of TACE or MMP activity. Recombinant TACE or MMP enzymes are incubated with a fluorogenic peptide substrate in the presence of varying concentrations of Apratastat. The cleavage of the substrate by the enzyme releases a fluorescent signal, which is measured over time. The IC50 for inhibition is calculated from the concentration-response curve. The compound's ability to inhibit TNF-α release is also assessed in cellular assays.
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| Cell Assay |
Cellular assays for Apratastat are performed in cells that produce TNF-α, such as macrophages or monocytes. Cells are stimulated with LPS to induce TNF-α production in the presence of varying concentrations of Apratastat. The levels of TNF-α in the culture supernatant are measured by ELISA, and the IC50 for inhibition of TNF-α release is calculated. Apratastat shows an IC50 of 144 ng/mL in vitro for inhibiting TNF-α release.
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| Animal Protocol |
In vivo animal studies with Apratastat have been performed in models of inflammatory diseases. In these studies, the compound is administered orally, and its effects on TNF-α levels and disease progression are assessed. Apratastat's ex vivo IC50 for inhibiting TNF-α release is 81.7 ng/mL. However, specific in vivo efficacy data, including animal models and detailed dosing regimens, are not extensively detailed in the available literature.
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| ADME/Pharmacokinetics |
Apratastat has a molecular weight of 414.5 and a molecular formula of C17H22N2O6S2. It is soluble in DMSO and other organic solvents. The compound is stable when stored as a powder at -20°C for up to 3 years or in solution at -80°C for up to 1 year. The compound is orally active, indicating good oral bioavailability. Detailed pharmacokinetic parameters are not extensively reported.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Apratastat are not extensively reported. The compound is classified as a research-use-only chemical and is not intended for human consumption. As a TACE and MMP inhibitor, it may have effects on normal physiological processes that could contribute to toxicity. Specific toxicological data, including acute toxicity, genotoxicity, and target organ effects, are not reported in the available literature.
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| References | |
| Additional Infomation |
Apratastat is a sulfonamide drug. Tmi-005 is currently being investigated in the clinical trial NCT00095342 (a study evaluating the efficacy of TMI-005 in active rheumatoid arthritis).
Apratastat is a research-grade compound not approved for clinical use. Its primary applications are in studying the role of TACE and MMPs in inflammatory diseases and cancer. The compound is used to investigate the therapeutic potential of TACE/MMP inhibition for the treatment of rheumatoid arthritis and other chronic inflammatory conditions. It is also used to study the potential of TACE/MMP inhibition to overcome radiotherapy resistance in non-small cell lung cancer. |
| Molecular Formula |
C17H22N2O6S2
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|---|---|
| Molecular Weight |
414.49638
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| Exact Mass |
414.091
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| CAS # |
287405-51-0
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| PubChem CID |
11452716
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.607
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| LogP |
1.42
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
683
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| Defined Atom Stereocenter Count |
1
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| SMILES |
OCC#CCOC1C=CC(S(N2CCSC(C)(C)[C@@H]2C(NO)=O)(=O)=O)=CC=1
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| InChi Key |
MAVDNGWEBZTACC-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C17H22N2O6S2/c1-17(2)15(16(21)18-22)19(9-12-26-17)27(23,24)14-7-5-13(6-8-14)25-11-4-3-10-20/h5-8,15,20,22H,9-12H2,1-2H3,(H,18,21)/t15-/m0/s1
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| Chemical Name |
(3S)-N-hydroxy-4-[4-(4-hydroxybut-2-ynoxy)phenyl]sulfonyl-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 : ~41.4 mg/mL (~99.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 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 25.0 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: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) 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. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.03 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 | 2.4125 mL | 12.0627 mL | 24.1255 mL | |
| 5 mM | 0.4825 mL | 2.4125 mL | 4.8251 mL | |
| 10 mM | 0.2413 mL | 1.2063 mL | 2.4125 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00095342 | COMPLETED | Drug: TMI-005 | Rheumatoid Arthritis | Wyeth is now a wholly owned subsidiary of Pfizer | 2005-08 | Phase 2 |
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