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Purity: ≥98%
| Targets |
Gosogliptin targets dipeptidyl peptidase-4 (DPP-4), a serine exopeptidase that rapidly degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 and GIP are released from the intestine in response to food intake and stimulate insulin secretion from pancreatic β-cells in a glucose-dependent manner. By inhibiting DPP-4, Gosogliptin prevents the degradation of these incretin peptides, prolonging their half-life and enhancing their insulinotropic effects. The compound is a competitive inhibitor of DPP-4, meaning it competes with the natural substrates for binding to the active site. Gosogliptin's selectivity for DPP-4 over other proteases contributes to its favorable safety profile.
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| ln Vitro |
Gosogliptin (PF-00734200) is a strong, selective, competitive, and oral active inhibitor of DPP-IV, the enzyme that breaks down the glucose-dependent insulinotropic polypeptide and the incretin peptide GLP-1. More than 200 times more selective than aminopeptidase P, fibroblast-activating proteins, propyl oligopeptidase, and other members of the DPP family (DPP-2, DPP-3, DPP-8, and DPP-9) is gosogliptin. comparable catalytic activity of the enzymes. Oral gosogliptin administration to rats, dogs, and monkeys causes a fast and reversible inhibition of plasma DPP-4 activity”. In a number of non-clinical animals, gologliptin increases insulin secretion and enhances glucose tolerance [2].
Gosogliptin demonstrates potent in vitro activity as a DPP-4 inhibitor. The compound is a highly selective and competitive inhibitor of DPP-4. In enzymatic assays, Gosogliptin effectively inhibits DPP-4 activity, preventing the degradation of GLP-1 and GIP. The compound's potency and selectivity make it a valuable tool for studying the role of DPP-4 in glucose homeostasis and incretin biology. Detailed IC50 values and enzymatic assay data are available in the primary literature. Gosogliptin's ability to enhance insulin secretion and lower blood glucose has been demonstrated in various in vitro systems. |
| ln Vivo |
This study aimed to evaluate the excretion, pharmacokinetics, and metabolism of [14C]gosogliptin in humans, beagle dogs, and Sprague-Dawley (SD) rats. Oral [14C]golagliptin dosages of 5 mg/kg were given to intact SD rats, 5 mg/kg to beagle dogs, and 20 mg to humans. After giving SD rats a single oral dose of [14C] Gosogliptin, urine, feces, and cage wash fluid contained, on average, 97.1% of the radioactivity after 168 hours. 66.0% was the average cumulative dosage recovered in feces. Urine has an average cumulative excretion rate of 30.8%. Within the first 48 hours, around 95% of the radioactivity expelled is recovered. In rats with bile duct cannulation, the average total recovery of dosed radioactivity was 29.5% in the urine and 62.0% in the bile. There were no variations in radioactive excretion patterns based on sex [2].
Gosogliptin demonstrates rapid and reversible inhibition of plasma DPP-4 activity when administered orally to rats, dogs, and monkeys. In various nonclinical models, Gosogliptin stimulates insulin secretion and improves glucose tolerance. The compound's oral activity and efficacy in animal models support its utility for studying DPP-4 inhibition as a therapeutic strategy for type 2 diabetes. Gosogliptin has been evaluated in animal studies for its effects on glucose tolerance and insulin secretion. Detailed in vivo efficacy data, including specific dosing regimens and glucose tolerance test results, are available in the primary literature. The compound's rapid and reversible inhibition of DPP-4 activity has been demonstrated across multiple species (rats, dogs, monkeys). |
| Enzyme Assay |
The in vitro enzyme inhibition assay for Gosogliptin measures the inhibition of DPP-4 enzymatic activity. Recombinant human DPP-4 enzyme is incubated with varying concentrations of Gosogliptin (typically ranging from nanomolar to micromolar) in the presence of a fluorescent or chromogenic substrate (e.g., Gly-Pro-p-nitroanilide). The enzymatic reaction is monitored by measuring the release of the fluorescent or chromogenic product. IC50 values are determined by fitting dose-response curves to the inhibition data. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. The competitive nature of inhibition can be confirmed by varying substrate concentrations. Appropriate positive controls (known DPP-4 inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for Gosogliptin is performed using cells that express DPP-4, such as human intestinal epithelial cells or lymphocytes. Cells are cultured in appropriate medium and treated with varying concentrations of Gosogliptin or vehicle control (DMSO). DPP-4 activity in cell lysates or on the cell surface is measured using a fluorescent or chromogenic substrate. The inhibition of DPP-4 activity is quantified, and IC50 values are determined. Alternatively, the compound's effects on GLP-1 degradation can be assessed by incubating cells with GLP-1 in the presence or absence of Gosogliptin and measuring the remaining GLP-1 levels by ELISA. The compound's effects on insulin secretion can be assessed using pancreatic β-cell lines.
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| Animal Protocol |
In vivo animal experiments with Gosogliptin are conducted using rodents (rats, mice), dogs, or monkeys. Gosogliptin is administered orally at various doses. Plasma DPP-4 activity is measured at various time points post-dose using a fluorometric or colorimetric assay to assess the rapid and reversible inhibition of DPP-4. For glucose tolerance tests, animals are fasted overnight and then administered Gosogliptin or vehicle control prior to an oral glucose challenge. Blood glucose and insulin levels are measured at various time points post-glucose administration to assess the compound's effects on glucose tolerance and insulin secretion. Body weight and general health status are monitored throughout the study.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for Gosogliptin are partially documented. The compound is orally active and demonstrates rapid inhibition of plasma DPP-4 activity. Gosogliptin has a molecular weight of 366.41 and a chemical formula of C17H24F2N6O. The compound is soluble in DMSO at 100 mg/mL (272.92 mM). For in vivo administration, a formulation of 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline can be used (≥5 mg/mL). The compound should be stored in a dry, dark place under an inert atmosphere at -20°C. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for Gosogliptin are not extensively documented in publicly available sources. As a research-grade compound, Gosogliptin is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References |
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| Additional Infomation |
Gosogliptin is an amino acid amide. Gosogliptin has been used in clinical trials for the treatment of chronic renal insufficiency. Gosogliptin is a potent, selective, and orally bioavailable difluoropyrrolidine dipeptidyl peptidase-4 (DPP-4) inhibitor with hypoglycemic activity.
Gosogliptin is a research compound developed for studying the role of DPP-4 in glucose homeostasis and for evaluating DPP-4 inhibition as a therapeutic strategy for type 2 diabetes. The compound is also known as PF-00734200. Gosogliptin is a potent, reversible, orally active, highly selective, and competitive DPP-4 inhibitor that increases GLP-1 and GIP levels, enhancing insulin secretion and lowering blood glucose. The compound has demonstrated rapid and reversible inhibition of plasma DPP-4 activity in rats, dogs, and monkeys, and has improved glucose tolerance in nonclinical models. Gosogliptin is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical metabolic research. Gosogliptin is available from various chemical suppliers for research purposes. |
| Molecular Formula |
C17H24N6OF2
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| Molecular Weight |
366.40886
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| Exact Mass |
366.198
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| CAS # |
869490-23-3
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| PubChem CID |
11516136
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| Appearance |
White to yellow solid powder
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| LogP |
0.466
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
508
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN(CC1(F)F)C(=O)[C@@H]2C[C@@H](CN2)N3CCN(CC3)C4=NC=CC=N4
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| InChi Key |
QWEWGXUTRTXFRF-KBPBESRZSA-N
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| InChi Code |
InChI=1S/C17H24F2N6O/c18-17(19)2-5-25(12-17)15(26)14-10-13(11-22-14)23-6-8-24(9-7-23)16-20-3-1-4-21-16/h1,3-4,13-14,22H,2,5-12H2/t13-,14-/m0/s1
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| Chemical Name |
(3,3-difluoropyrrolidin-1-yl)((2S,4S)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidin-2-yl)methanone
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| Synonyms |
PF-00734200; PF 00734200; PF00734200; PF-734200; PF 734200; PF734200;
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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 | 2.7292 mL | 13.6459 mL | 27.2918 mL | |
| 5 mM | 0.5458 mL | 2.7292 mL | 5.4584 mL | |
| 10 mM | 0.2729 mL | 1.3646 mL | 2.7292 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03088670
Conditions:Diabetes Mellitus, Type 2Link: https://clinicaltrials.gov/ct2/show/NCT00596518
Conditions:Renal Insufficiency, ChronicLink: https://clinicaltrials.gov/ct2/show/NCT00618007
Conditions:Diabetes Mellitus, Type 2
Title:12 Week Study Of PF-00734200 For The Treatment Of Type 2 Diabetes Mellitus In Subjects Treated With Metformin
Status:Completed
updateDate:2010-06-24
Ctid:NCT00473525
Link: https://clinicaltrials.gov/ct2/show/NCT00473525
Conditions:Diabetes Mellitus, Type 2 Median concentration–time profiles by varying degrees of renal function (linear-linear).Br J Clin Pharmacol.2011 Jul;72(1):85-91. |
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 Median concentration–time profiles by varying degrees of renal function (log-linear).Br J Clin Pharmacol.2011 Jul;72(1):85-91. |
 Regression and 90% confidence intervals of serum PF-734200 CLu/F vs.CLcr.Br J Clin Pharmacol.2011 Jul;72(1):85-91. |
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