| 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 |
IC50: 20±10 μM (MMP)[1]; Ki: 1.5±0.27 nM (MMPs)[1]
The compound targets matrix metalloproteinases (MMPs), TACE (ADAM17), and other ADAMs. It inhibits MMPs with an IC50 of 20±10 μM. It binds to hmeprin with inhibitory constants (IC50) of 20±10 μM for the β subunit and 1.5±0.27 nM for the α subunit. By inhibiting these enzymes, it modulates the shedding of membrane-bound proteins and cytokine processing. |
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| ln Vitro |
The hydroxamate-based metalloproteinase inhibitor TAPI-2 binds to hmeprin; its inhibitory constants (IC50) are 20±10 μM for the hmeprin β subunit and 1.5±0.27 nM for the hmeprin α subunit, respectively. Generally speaking, the α subunit exhibits stronger inhibition than the β subunit [1]. Without changing the expression of ADAM17, TAPI-2 dramatically lowered the protein levels of NICD and its downstream target HES-1 in HCP-1 and HT29 cells. Additionally, TAPI-2 treatment of the cells markedly decreased the CSC phenotype in both CRC cell lines by -50%. The established dose range of TAPI-2 (5-40 μM) was not exceeded by the concentration employed (20 μM), as demonstrated by the dose-dependent effects of TAPI-2 on spheroid formation and protein levels of NICD and HES-1 [3].
In vitro, TAPI-2 dramatically lowers the protein levels of NICD and its downstream target HES-1 in HCP-1 and HT29 cells without changing the expression of ADAM17. It markedly decreases the cancer stem cell (CSC) phenotype in CRC cell lines by ~50% at 20 μM. It inhibits the activation-induced shedding of L-selectin from neutrophils, eosinophils, and lymphocytes. |
| ln Vivo |
In vivo activity of TAPI-2 is not extensively detailed. As a broad-spectrum metalloprotease inhibitor, it would be expected to modulate shedding of various cell surface proteins and cytokine processing. It has been used in studies of viral envelope shedding and cytokine modulation. Specific in vivo efficacy data are not provided in the available literature.
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| Enzyme Assay |
In vitro enzyme assays for TAPI-2 involve measuring MMP, TACE, or ADAM activity. Recombinant enzymes are incubated with peptide substrates and varying concentrations of TAPI-2. Enzyme activity is quantified by measuring cleavage of the substrate using fluorometric or colorimetric methods. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
TAPI-2 is dissolved in DMSO and diluted with appropriate medium before use. All experiments are performed using 20 μM TAPI-2. Cells are cultured with or without TAPI-2 for 48 hours and then seeded at 3,000 cells per well in 96-well plates. After pretreatment, increasing doses of 5-fluorouracil (5-FU) that are relevant to the recommended clinical dose (up to 2 μg/mL) are added, with or without TAPI-2, for 72 hours. Cell viability is assessed by adding MTT substrate (0.25% in phosphate-buffered saline [PBS]) in growth medium (1:5 dilution) to cells for 1 hour at 37°C. The cells are ished with PBS, and 100 μL of dimethyl sulfoxideis added. Optical density is measured at 570 nM, and relative MTT is presented as a percentage of control[2].
For in vitro cell-based assays, cancer cell lines such as HCP-1 and HT29 are cultured and treated with TAPI-2 at 20 μM for 48 hours. NICD and HES-1 protein levels are measured by Western blot. CSC phenotype is assessed by spheroid formation assays. Cell viability is assessed using MTT assays. |
| ADME/Pharmacokinetics |
TAPI-2 (CAS 187034-31-7) has a molecular formula of C19H37N5O5 and a molecular weight of 415.53. It is a white to off-white solid powder. It is soluble in DMSO. It should be stored under recommended conditions. Detailed pharmacokinetic parameters are not extensively characterized in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicity data for TAPI-2 are not extensively provided. As a metalloprotease inhibitor, it would be expected to have a safety profile related to modulation of shedding and cytokine processing. The compound is for research use only and is not for human or clinical use. Standard toxicology assessments would be required.
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| References |
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| Additional Infomation |
TAPI-2 is a hydroxamate-based inhibitor of MMPs and TACE. It inhibits the activation-induced shedding of L-selectin from neutrophils, eosinophils, and lymphocytes. It is used to study metalloprotease inhibition, viral envelope shedding, and cytokine modulation. No approved therapeutic status is reported.
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| Molecular Formula |
C19H37N5O5
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|---|---|
| Molecular Weight |
415.5276
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| Exact Mass |
415.279
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| CAS # |
187034-31-7
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| Related CAS # |
(R)-TAPI-2;689284-12-6
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| PubChem CID |
1620
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Index of Refraction |
1.506
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| LogP |
-0.55
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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 |
12
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| Heavy Atom Count |
29
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| Complexity |
574
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)CC(CC(=O)NO)C(=O)NC(C(=O)NC(C)C(=O)NCCN)C(C)(C)C
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| InChi Key |
LMIQCBIEAHJAMZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H37N5O5/c1-11(2)9-13(10-14(25)24-29)17(27)23-15(19(4,5)6)18(28)22-12(3)16(26)21-8-7-20/h11-13,15,29H,7-10,20H2,1-6H3,(H,21,26)(H,22,28)(H,23,27)(H,24,25)
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| Chemical Name |
N-[1-[[1-(2-aminoethylamino)-1-oxopropan-2-yl]amino]-3,3-dimethyl-1-oxobutan-2-yl]-N'-hydroxy-2-(2-methylpropyl)butanediamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O : ~100 mg/mL (~240.66 mM)
Ethanol : ~50 mg/mL (~120.33 mM) DMSO : ≥ 22 mg/mL (~52.94 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.01 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 20.8 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: ≥ 2.08 mg/mL (5.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4066 mL | 12.0328 mL | 24.0657 mL | |
| 5 mM | 0.4813 mL | 2.4066 mL | 4.8131 mL | |
| 10 mM | 0.2407 mL | 1.2033 mL | 2.4066 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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