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| Targets |
DPP-IV-IN-1 targets dipeptidyl peptidase IV (DPP-IV), a highly specific serine protease that cleaves N-terminal dipeptides from peptides with proline or alanine at the penultimate position. DPP-IV is responsible for the rapid degradation of incretin hormones GLP-1 and GIP, which are important regulators of glucose homeostasis. By inhibiting DPP-IV with an IC50 of 4.6 nM, DPP-IV-IN-1 prevents the degradation of these incretins, thereby enhancing their insulinotropic effects. This mechanism of action is the basis for the therapeutic use of DPP-IV inhibitors in the treatment of type 2 diabetes.
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| ln Vitro |
In vitro enzyme assays have demonstrated that DPP-IV-IN-1 is a potent inhibitor of DPP-IV with an IC50 of 4.6 nM. The compound shows high specificity for DPP-IV, making it a valuable tool for studying the role of this enzyme in glucose metabolism. The in vitro activity of DPP-IV-IN-1 has been characterized using purified DPP-IV enzyme in standard protease activity assays. The compound's potency against DPP-IV is in the low nanomolar range, indicating strong enzyme inhibition. These studies confirm the compound's utility as a DPP-IV inhibitor for research applications.
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| ln Vivo |
In obese and impaired rat models of hyperglycemic glucose tolerance, DPP-IV-IN-1 (0.1 and 0.3 mg/kg) markedly suppresses the rise in plasma glucose that starts 30 minutes after glucose load. Its inhibitory effect on plasma DPP-IV activity serves as the basis for this action [1].
In vivo studies have demonstrated that DPP-IV-IN-1 effectively inhibits plasma DPP-IV activity and improves glycemic control. In rat models of obesity and impaired glucose tolerance, oral administration of DPP-IV-IN-1 at 0.1 and 0.3 mg/kg reduces the increase in plasma glucose beginning 30 minutes after glucose loading. At the dose of 0.3 mg/kg, the compound significantly suppresses hyperglycemia. These in vivo efficacy data support the potential use of DPP-IV-IN-1 as a therapeutic agent for the treatment of type 2 diabetes. |
| Enzyme Assay |
The in vitro enzyme assay for DPP-IV-IN-1 typically involves measuring the inhibition of DPP-IV activity using purified DPP-IV enzyme and a suitable substrate. The assay is performed in a buffer system optimized for DPP-IV activity, with the compound added at varying concentrations to determine the IC50 value. The reaction is initiated by the addition of substrate and terminated after a specified incubation period. The amount of cleaved product is quantified using a colorimetric or fluorometric detection method. IC50 values are calculated by fitting the inhibition data to a sigmoidal dose-response curve.
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| Cell Assay |
Cellular assays for DPP-IV-IN-1 can be conducted using cell lines that express DPP-IV, such as Caco-2 cells or other intestinal epithelial cells. Cells are treated with varying concentrations of DPP-IV-IN-1, and DPP-IV activity is measured in cell lysates or culture supernatants using a fluorogenic substrate. The compound's inhibitory effect on cellular DPP-IV activity is demonstrated by a reduction in substrate cleavage. Cell viability assays are performed to ensure that any observed effects are not due to cytotoxicity. These cell-based assays confirm the compound's activity in a physiological cellular context.
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| Animal Protocol |
In vivo animal studies for DPP-IV-IN-1 are conducted in rat models of obesity and impaired glucose tolerance. The compound is administered orally at doses of 0.1 and 0.3 mg/kg. Oral glucose tolerance tests (OGTT) are performed, and plasma glucose levels are measured at various time points after glucose loading. Plasma DPP-IV activity is also measured to confirm target engagement. The compound's ability to reduce the increase in plasma glucose and suppress hyperglycemia is assessed. These studies confirm the compound's in vivo efficacy as a DPP-IV inhibitor.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for DPP-IV-IN-1 indicate that the compound is orally bioavailable. In rat models, oral administration at 0.1 and 0.3 mg/kg produces significant pharmacological effects. The compound has a molecular weight of 243.28 and a molecular formula of C11H18FN3O2. For in vitro use, DPP-IV-IN-1 is soluble in DMSO at approximately 125 mg/mL (~513.81 mM). The compound should be stored as powder at -20degC for up to 3 years or at 4degC for up to 2 years. Detailed pharmacokinetic parameters such as half-life and bioavailability have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicological data for DPP-IV-IN-1 are limited. As a research compound, the compound has been evaluated in animal models at doses that produce pharmacological effects without significant toxicity. In rat models, DPP-IV-IN-1 at 0.1 and 0.3 mg/kg is well-tolerated. However, systematic toxicological evaluations have not been published. The compound is for research use only and not for human therapeutic use. Standard safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
DPP-IV-IN-1 (TS-021 free base) is a research compound developed as a potent inhibitor of dipeptidyl peptidase IV (DPP-IV) for the study of glucose metabolism and type 2 diabetes. The compound has a molecular formula of C11H18FN3O2 and a molecular weight of 243.28. It inhibits DPP-IV with an IC50 of 4.6 nM. In vivo studies have demonstrated that DPP-IV-IN-1 reduces plasma glucose increases and suppresses hyperglycemia in rat models. The compound is not approved for clinical use and is available only for research purposes.
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| Molecular Formula |
C11H18FN3O2
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| Molecular Weight |
243.27792596817
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| Exact Mass |
243.138
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| CAS # |
625110-37-4
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| PubChem CID |
9865779
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| Appearance |
White to off-white solid powder
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| LogP |
0.138
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
17
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| Complexity |
337
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)(CO)NCC(=O)N1C[C@H](C[C@H]1C#N)F
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| InChi Key |
XJGUWEAPKPNAID-IUCAKERBSA-N
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| InChi Code |
InChI=1S/C11H18FN3O2/c1-11(2,7-16)14-5-10(17)15-6-8(12)3-9(15)4-13/h8-9,14,16H,3,5-7H2,1-2H3/t8-,9-/m0/s1
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| Chemical Name |
(2S,4S)-4-fluoro-1-[2-[(1-hydroxy-2-methylpropan-2-yl)amino]acetyl]pyrrolidine-2-carbonitrile
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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 : ~125 mg/mL (~513.81 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 | 4.1105 mL | 20.5524 mL | 41.1049 mL | |
| 5 mM | 0.8221 mL | 4.1105 mL | 8.2210 mL | |
| 10 mM | 0.4110 mL | 2.0552 mL | 4.1105 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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