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| 5mg |
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| Targets |
(S,S)-TAPI-1 targets tumor necrosis factor-α converting enzyme (TACE), also known as ADAM17, a zinc metalloprotease. It also inhibits other matrix metalloproteinases (MMPs). By inhibiting TACE, it prevents the cleavage of membrane-bound precursors, thereby blocking the release of soluble TNF-α and other cell-surface proteins like TNF receptors (TNFRs) and IL-6R.
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| ln Vitro |
In vitro, TAPI-1 inhibits the cleavage of TNF-α with an IC50 of approximately 100 nM in a TNF peptide cleavage assay. It also inhibits the TACE-dependent constitutive release of sAPPα (soluble amyloid precursor protein alpha) with an IC50 of 8.09 μM, and the M3 muscarinic receptor-stimulated release with an IC50 of 3.61 μM in HEK293 cells. Furthermore, TAPI-1 prevents the PMA-induced shedding of TNF-α, p60 TNFR, and IL-6R in monocytic cell lines and peripheral blood mononuclear cells.
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| ln Vivo |
In vivo, TAPI-1 has been shown to inhibit TACE and other metalloproteases. In a mouse model of LPS-induced acute kidney injury, treatment with TAPI-1 was able to modulate the increase in serum creatinine, TNFα, and urinary biomarkers, suggesting a protective effect against kidney damage. Its stability in vivo makes it suitable for such studies.
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| Enzyme Assay |
The non-cellular enzyme/receptor binding assay for (S,S)-TAPI-1 typically involves measuring its inhibition of TACE/ADAM17 activity. In a typical protocol, a recombinant or purified TACE enzyme is incubated with a fluorogenic or colorimetric peptide substrate in the presence of varying concentrations of the inhibitor. The cleavage of the substrate, which releases a fluorescent or chromogenic signal, is measured over time using a microplate reader. The IC50, the concentration required to inhibit 50% of the enzyme activity, is calculated from the dose-response curve.
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| Cell Assay |
In vitro cellular assays for (S,S)-TAPI-1 often utilize cell lines that naturally shed proteins of interest, such as THP-1 monocytes or HEK-293 cells. Cells are seeded in multi-well plates and pre-treated with TAPI-1 at various concentrations. Shedding is then stimulated (e.g., with PMA in THP-1 cells or via M3 receptor activation in HEK-293 cells). The amount of shed protein (e.g., TNF-α, sAPPα) in the cell culture supernatant is quantified by ELISA or immunoblotting. Cell viability is concurrently assessed using assays like CellTiter-Glo to ensure the observed effects are not due to cytotoxicity.
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| Animal Protocol |
In vivo animal studies for (S,S)-TAPI-1 typically involve rodent models of disease. For example, in a study on acute kidney injury, male Sprague-Dawley rats were used. The compound was administered via intracerebroventricular (i.c.v.) injection at a dose of 1 μg. In another model, mice were treated with lipopolysaccharide (LPS) (10 mg/kg, i.p.) to induce systemic inflammation, and the effect of TAPI-1 on inflammatory markers and organ damage was assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of (S,S)-TAPI-1 are not extensively detailed in standard product information, but it is characterized as being more stable in vivo than its analog TAPI-0. This enhanced stability is a key feature that makes it suitable for in vivo applications. It is soluble in DMF, DMSO, and ethanol at 30 mg/mL, and in PBS (pH 7.2) at 10 mg/mL.
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| Toxicity/Toxicokinetics |
Specific toxicological data for (S,S)-TAPI-1 are not extensively available in standard product documentation. As a research-use compound, comprehensive toxicity profiles are not typically provided. However, it is generally handled as a potential irritant, and standard laboratory safety precautions should be observed. Its use is restricted to in vitro and in vivo research, and it is not intended for human therapeutic use.
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| References |
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| Additional Infomation |
(S,S)-TAPI-1 is a research-grade compound intended for laboratory use only and is not approved for clinical use. Its primary research applications include studying the role of TACE/ADAM17 in the shedding of TNF-α and other cell-surface proteins, investigating inflammatory pathways, and exploring potential therapeutic targets for diseases like arthritis and kidney damage. Its CAS number is 171235-71-5, and its molecular formula is C₂₆H₃₇N₅O₅.
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| Molecular Formula |
C26H37N5O5
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|---|---|
| Molecular Weight |
499.602486371994
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| Exact Mass |
499.279
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| CAS # |
171235-71-5
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| Related CAS # |
TAPI-1;163847-77-6
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| PubChem CID |
9827273
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.581
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| LogP |
1.29
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
36
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| Complexity |
746
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H](C(=O)NCCN)NC(=O)[C@H](CC1=CC2=CC=CC=C2C=C1)NC(=O)C(CC(C)C)CC(=O)NO
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.0016 mL | 10.0080 mL | 20.0160 mL | |
| 5 mM | 0.4003 mL | 2.0016 mL | 4.0032 mL | |
| 10 mM | 0.2002 mL | 1.0008 mL | 2.0016 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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