| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 7 nM (TPP II) and 10 μM (TPP I)[1]
The compound specifically targets tripeptidyl peptidase II (TPP II), a large serine protease responsible for the stepwise removal of tripeptides from the N-terminus of protein substrates. It is also known as the CCK-inactivating peptidase that degrades the neuropeptide cholecystokinin-8 (CCK-8), which regulates satiety, digestion, and anxiety. |
|---|---|
| ln Vitro |
TPP II activity of cerebral membranes is inhibited by butabindide (UCL-1397; 0-24 nM; membranes of rat cerebral cortex) oxalate[2].
In biochemical assays, Butabindide oxalate shows potent inhibition of TPP II with a Ki value of 7 nM. It is highly selective for TPP II over TPP I, exhibiting a Ki of 10 microM for TPP I (over 1,400-fold selectivity). This selectivity makes it an ideal tool for dissecting the specific roles of TPP II in peptide metabolism, particularly for protecting CCK-8 against inactivation. |
| ln Vivo |
Inhibiting the breakdown of CCK-8 in the gastrointestinal tract, butabindide (UCL-1397; 10 mg/kg; iv; for 20 min) oxalate enhances mice's satiety[2].
In vivo, Butabindide oxalate inhibits TPP II activity in the gastrointestinal tract. Following intravenous administration, it has an ID50 of 1.1 mg/kg for inhibiting liver TPP II and 6.8 mg/kg for brain TPP II. By protecting CCK-8 from degradation, it enhances satiety and reduces food intake in animal models, as demonstrated when administered at 10 mg/kg iv for 20 minutes. |
| Enzyme Assay |
A non-cellular protease assay is used to determine TPP II activity. Recombinant human TPP II (or purified rat liver enzyme) is incubated with a fluorogenic tripeptide substrate (e.g., H-Ala-Ala-Phe-AMC or succinyl-Ala-Ala-Ala-AMC) in assay buffer at pH 7.4. Butabindide oxalate is added at varying concentrations (0.1-1000 nM), and the reaction is monitored by fluorescence (ex/em ~380/460 nm). The Ki value is calculated from competitive inhibition kinetics.
|
| Cell Assay |
Cell-based assays for TPP II activity involve the use of cell lysates. Tissues or cells (e.g., neurons, glial cells, or gastrointestinal epithelial cells) are homogenized in buffer containing 0.1% Triton X-100. The lysate is clarified by centrifugation, and the supernatant is incubated with a fluorogenic TPP II substrate (e.g., Ala-Ala-Phe-AMC) at 37degC for 30-60 minutes. Butabindide oxalate is added to the lysate to confirm the specificity of TPP II-mediated substrate cleavage.
|
| Animal Protocol |
Animal/Disease Models: Mice (25-30 g)[2]
Doses: 10 mg/kg Route of Administration: intravenous (iv) injection; for 20 minutes Experimental Results: Reduces food intake and elicits other behavioral concomitants of satiation. In vivo, Butabindide oxalate is used in a mouse satiety/food intake model. Male Sprague-Dawley rats or C57BL/6 mice are fasted overnight. Butabindide oxalate (1-10 mg/kg) is administered via intravenous (iv) injection or intraperitoneally (ip) 15-30 minutes before refeeding. Food intake is measured at 1, 2, 4, and 24 hours post-refeeding. A reduction in cumulative food intake indicates TPP II inhibition and increased CCK-8 bioavailability. To measure enzyme inhibition directly, animals are euthanized at 20-60 minutes post-dose, and liver and brain tissues are harvested for ex vivo TPP II activity assays. |
| ADME/Pharmacokinetics |
Butabindide oxalate has a molecular weight of 393.44 (C17H25N3O2·C2H2O4). As a peptide-derived inhibitor, it is likely to have poor oral bioavailability due to proteolytic degradation in the GI tract. Therefore, it is typically administered intravenously in research models. It is stable as a powder when desiccated at -20degC. Its plasma half-life is expected to be short (on the order of minutes to an hour).
|
| Toxicity/Toxicokinetics |
Specific toxicity data for Butabindide oxalate is limited. In animal studies at effective doses (1-10 mg/kg iv), it was well-tolerated with no reported acute mortality. As a selective protease inhibitor, it is not expected to be highly cytotoxic. However, chronic effects on CCK-8 signaling have not been extensively studied. The compound is for research use only and not for human clinical therapy.
|
| References |
[1]. Ganellin CR, et, al. Inhibitors of tripeptidyl peptidase II. 3. Derivation of butabindide by successive structure optimizations leading to a potential general approach to designing exopeptidase inhibitors. J Med Chem. 2005 Nov 17;48(23):7333-42.
[2]. Rose C, et, al. Characterization and inhibition of a cholecystokinin-inactivating serine peptidase. Nature. 1996 Apr 4;380(6573):403-9. |
| Additional Infomation |
Butabindide oxalate is a lead compound developed by University College London (UCL) for studying TPP II. It is also known as UCL-1397 and is sold with the permission of INSERM and UCL. Its IUPAC name is (S)-1-((S)-2-aminobutanoyl)-N-butylindoline-2-carboxamide oxalate. It has been used in studies of c-MYC-induced centriole overduplication and antigen processing, demonstrating utility beyond neuropeptide regulation.
|
| Molecular Formula |
C19H27N3O6
|
|---|---|
| Molecular Weight |
393.43
|
| Exact Mass |
393.19
|
| CAS # |
185213-03-0
|
| Related CAS # |
Butabindide;175553-48-7
|
| PubChem CID |
56972132
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.359
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
28
|
| Complexity |
471
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CCCCNC([C@@H]1CC2=CC=CC=C2N1C([C@H](CC)N)=O)=O.OC(C(=O)O)=O
|
| InChi Key |
KKMJFDVOXSGHBF-SLHAJLBXSA-N
|
| InChi Code |
InChI=1S/C17H25N3O2.C2H2O4/c1-3-5-10-19-16(21)15-11-12-8-6-7-9-14(12)20(15)17(22)13(18)4-2;3-1(4)2(5)6/h6-9,13,15H,3-5,10-11,18H2,1-2H3,(H,19,21);(H,3,4)(H,5,6)/t13-,15-;/m0./s1
|
| Chemical Name |
(2S)-1-[(2S)-2-aminobutanoyl]-N-butyl-2,3-dihydroindole-2-carboxamide;oxalic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O: 39 mg/mL (99.13 mM)
|
|---|---|
| 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 | 2.5417 mL | 12.7087 mL | 25.4175 mL | |
| 5 mM | 0.5083 mL | 2.5417 mL | 5.0835 mL | |
| 10 mM | 0.2542 mL | 1.2709 mL | 2.5417 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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