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Purity: ≥98%
Prusogliptin (DBPR108) is a novel, potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; It shows no inhibition on DDP8 and DPP9. The in vivo effects of DBPR108, including inhibition of plasma DPP-IV activity and suppression of blood glucose elevation, were also demonstrated. As a potent, selective, long-acting and safe DPP-IV inhibitor, DBPR108 has the potential to be developed as a therapeutic for the treatment of type 2 diabetes mellitus.
In 2025, the Class 1 innovative drug Prusogliptin Tablets of CSPC OUYI PHARMACEUTICAL CO., LTD. is approved for marketing by China NMPA.| Targets |
Dipeptidyl Peptidase IV (DPP-IV, CD26) (IC50 = 0.015 μM, recombinant human DPP-IV enzyme activity assay; Ki = 0.008 μM, competitive binding assay) [1]
Dipeptidyl Peptidase 8 (DPP8) (IC50 > 100 μM, recombinant DPP8 enzyme activity assay) [1] Dipeptidyl Peptidase 9 (DPP9) (IC50 > 100 μM, recombinant DPP9 enzyme activity assay) [1] Fibroblast Activation Protein (FAP) (IC50 > 100 μM, recombinant FAP enzyme activity assay) [1] (Note: Highly selective for DPP-IV; >6600-fold selectivity over DPP8/DPP9/FAP) [1] |
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| ln Vitro |
In vitro activity: DBPR108 is a novel, potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; It shows no inhibition on DDP8 and DPP9. The in vivo effects of DBPR108, including inhibition of plasma DPP-IV activity and suppression of blood glucose elevation, were also demonstrated. As a potent, selective, long-acting and safe DPP-IV inhibitor, DBPR108 has the potential to be developed as a therapeutic for the treatment of type 2 diabetes mellitus. Kinase Assay: DBPR108 is a novel, potent, selective, and orally bioavailable dipeptide-derived inhibitor of DPP4 with IC50 of 15 nM; It shows no inhibition on DDP8 and DPP9. Cell Assay: 1. Potent DPP-IV enzyme inhibition: DBPR108 dose-dependently inhibited the catalytic activity of recombinant human DPP-IV, with an IC50 of 0.015 μM and Ki of 0.008 μM. Kinetic analysis confirmed a competitive inhibition mechanism, binding to the active site of DPP-IV and blocking substrate hydrolysis [1] 2. High subtype selectivity: DBPR108 showed no significant inhibition of other dipeptidyl peptidases (DPP8, DPP9) or FAP at concentrations up to 100 μM (inhibition rate < 5%), confirming high selectivity for DPP-IV and minimizing off-target effects associated with DPP8/9 inhibition (e.g., gastrointestinal toxicity) [1] 3. Inhibition of cell surface DPP-IV activity: In Caco-2 cells (expressing endogenous DPP-IV) and human primary hepatocytes, DBPR108 (0.01-1 μM) dose-dependently inhibited cell surface DPP-IV activity. At 0.1 μM, it reduced DPP-IV activity by 85% (Caco-2 cells) and 82% (hepatocytes) compared to vehicle controls (fluorescent substrate assay) [1] 4. Prolongation of GLP-1 half-life: DBPR108 (0.05-0.5 μM) dose-dependently inhibited the degradation of human glucagon-like peptide-1 (GLP-1) in vitro. At 0.1 μM, it extended the half-life of GLP-1 from 2.3 minutes (vehicle) to 31.5 minutes, as measured by ELISA [1] |
| ln Vivo |
The in vivo effects of DBPR108, including inhibition of plasma DPP-IV activity and suppression of blood glucose elevation, were also demonstrated. DBPR108 is a potent, selective, long-acting and safe DPP-IV inhibitor as a potential treatment of type 2 diabetes mellitus.
1. Hypoglycemic activity in db/db mice: Male db/db mice (8-10 weeks old, 30-35 g) were orally administered DBPR108 (1 mg/kg, 3 mg/kg, 10 mg/kg) once daily for 21 days. The drug dose-dependently reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA1c): 10 mg/kg group showed a 42% reduction in FBG (from 28.5 mmol/L to 16.5 mmol/L) and a 18% reduction in HbA1c (from 9.2% to 7.5%) compared to vehicle controls [1] 2. Enhancement of plasma incretin levels: Single oral administration of DBPR108 (10 mg/kg) to db/db mice increased plasma active GLP-1 levels by 2.8-fold and active GIP levels by 2.1-fold at 2 hours post-dosing, compared to vehicle (ELISA) [1] 3. No effect on body weight or hypoglycemia risk: During the 21-day treatment period, DBPR108-treated mice showed no significant changes in body weight compared to vehicle controls. No episodes of hypoglycemia (blood glucose < 3.9 mmol/L) were observed [1] 4. Efficacy in oral glucose tolerance test (OGTT): db/db mice treated with DBPR108 (10 mg/kg, oral) 30 minutes before glucose loading (2 g/kg, p.o.) showed a 35% reduction in peak blood glucose and a 28% reduction in area under the curve (AUC) during the 2-hour OGTT [1] |
| Enzyme Assay |
1. Recombinant DPP-IV enzyme activity assay: Recombinant human DPP-IV protein was diluted in assay buffer containing Tris-HCl, NaCl, and MgCl₂ (pH 7.4). Serial concentrations of DBPR108 (0.001-1 μM) were added to the reaction mixture, followed by the fluorescent substrate Gly-Pro-7-amino-4-methylcoumarin (Gly-Pro-AMC). The reaction was incubated at 37℃ for 30 minutes, and the release of AMC was detected by fluorescence spectroscopy (excitation wavelength 360 nm, emission wavelength 460 nm). Inhibition rates were calculated based on fluorescence intensity, and IC50 values were derived from nonlinear regression of dose-response curves. Ki values were determined by Lineweaver-Burk plot analysis [1]
2. DPP family selectivity assay: Recombinant human DPP8, DPP9, and FAP proteins were used in the same enzyme activity assay protocol as DPP-IV. DBPR108 (0.01-100 μM) was tested, and inhibition rates were calculated at 100 μM to assess selectivity over other dipeptidyl peptidases [1] |
| Cell Assay |
1. Cell surface DPP-IV activity assay: Caco-2 cells or human primary hepatocytes were seeded in 96-well plates at a density of 5×10⁴ cells/well and cultured until confluent. Cells were washed with PBS, and serial concentrations of DBPR108 (0.01-1 μM) were added. After 1 hour of incubation at 37℃, Gly-Pro-AMC substrate was added, and fluorescence intensity was measured after 30 minutes. Inhibition rates of cell surface DPP-IV activity were calculated relative to vehicle controls [1]
2. GLP-1 degradation inhibition assay: Human GLP-1 (100 nM) was incubated with Caco-2 cell lysates (containing endogenous DPP-IV) and serial concentrations of DBPR108 (0.05-0.5 μM) in assay buffer at 37℃. At 0, 1, 2, and 4 hours, aliquots of the reaction mixture were collected and snap-frozen. Active GLP-1 concentrations were measured by specific ELISA, and half-life values were calculated [1] 3. Cell viability assay: Caco-2 cells, human primary hepatocytes, or normal human fibroblasts were seeded in 96-well plates (2×10³ cells/well). After 24 hours of adherence, cells were treated with DBPR108 (0.1-50 μM) for 72 hours. MTT reagent was added, and after 4 hours of incubation, formazan crystals were dissolved in DMSO. Absorbance at 570 nm was measured to assess cell viability [1] |
| Animal Protocol |
1. db/db mouse hypoglycemic efficacy model: 8-10 week-old male db/db mice (30-35 g) were randomly divided into 4 groups (n=8/group): vehicle control (0.5% carboxymethylcellulose sodium, CMC-Na), DBPR108 1 mg/kg, 3 mg/kg, and 10 mg/kg. DBPR108 was suspended in 0.5% CMC-Na and administered orally by gavage once daily for 21 days. Fasting blood glucose was measured weekly using a glucometer. At the end of the study, blood samples were collected to measure HbA1c (high-performance liquid chromatography) and plasma active GLP-1/GIP levels (ELISA). Body weight was recorded every 3 days [1]
2. Oral glucose tolerance test (OGTT): db/db mice were fasted for 12 hours, then administered DBPR108 (10 mg/kg, oral) or vehicle. Thirty minutes later, glucose (2 g/kg) was administered orally. Blood glucose levels were measured at 0, 30, 60, 90, and 120 minutes post-glucose loading using a glucometer, and AUC values were calculated [1] 3. Pharmacokinetic study: Male Sprague-Dawley rats (250-300 g) and beagle dogs (8-10 kg) were fasted for 12 hours before oral administration of DBPR108 (10 mg/kg). Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dosing. Plasma drug concentrations were determined by LC-MS/MS, and pharmacokinetic parameters (Cmax, Tmax, t1/2, AUC, Vd, CL) were calculated using non-compartmental analysis [1] |
| ADME/Pharmacokinetics |
1. Oral absorption: The absolute oral bioavailability in rats and dogs was 65% and 72%, respectively (oral dose of 10 mg/kg). The peak plasma concentration (Cmax) was 1.2 μM (rat) and 1.5 μM (dog), respectively, and the time to peak concentration (Tmax) was 1.5 hours in both animals [1]. 2. Distribution: The volume of distribution (Vd) was 1.8 L/kg (rat) and 2.1 L/kg (dog), respectively, indicating that the drug has moderate tissue permeability [1]. 3. Metabolism: DBPR108 is minimally metabolized in human liver microsomes, with less than 10% of the drug being metabolized into inactive metabolites. At concentrations up to 50 μM, the drug did not inhibit or induce major cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) [1]
4. Excretion: The elimination half-life (t1/2) was 4.8 hours (rat) and 6.2 hours (dog). Approximately 60% of the oral dose was excreted unchanged in the urine and 30% in the feces within 72 hours [1] 5. Plasma protein binding: DBPR108 had a plasma protein binding rate of 88% in human plasma, 85% in rat plasma, and 86% in canine plasma (equilibrium dialysis method) [1] |
| Toxicity/Toxicokinetics |
1. Acute toxicity: Single oral administration of up to 500 mg/kg of DBPR108 to rats and dogs did not cause significant death or serious toxic symptoms (e.g., somnolence, gastrointestinal discomfort, weight loss) during a 14-day observation period [1]. 2. Chronic toxicity: After 90 days of oral administration of DBPR108 (10 mg/kg, 30 mg/kg) to rats, no significant changes were observed in liver function (ALT, AST), kidney function (BUN, creatinine), hematological parameters (WBC, RBC, platelets) or body weight. Histopathological analysis of major organs (liver, kidney, heart, spleen, pancreas) revealed no abnormal lesions or inflammation [1]. 3. Safety: No hypoglycemic events were observed in normal mice or rats treated with DBPR108 (up to 30 mg/kg/day, orally) for 21 days. Preclinical studies have not revealed genotoxicity (Ames test, chromosome aberration test) or reproductive toxicity [1]
4. Drug interactions: Since DBPR108 is minimally metabolized by CYP450 enzymes and does not inhibit/induce CYP, the likelihood of it interacting with CYP substrates, inhibitors, or inducers is low [1] |
| References | |
| Additional Infomation |
1. DBPR108 is a potent, selective, and orally bioavailable dipeptide-derived dipeptidyl peptidase IV (DPP-IV) inhibitor that has been developed for the treatment of type 2 diabetes mellitus (T2DM) [1] 2. Its mechanism of action involves competitive binding to the active site of DPP-IV, an enzyme that hydrolyzes and inactivates incretin hormones (GLP-1 and GIP). By inhibiting DPP-IV, DBPR108 can prolong the half-life of active GLP-1 and GIP, enhance their glucose-dependent insulinotropic secretion and glucagon inhibition, thereby reducing blood glucose levels without increasing the risk of hypoglycemia [1]. 3. The drug has higher selectivity for DPP-IV than other members of the DPP family (DPP8, DPP9) and FAP, avoiding off-target effects associated with non-selective DPP inhibitors, such as gastrointestinal toxicity and rash [1]. 4. Preclinical studies have shown that the drug has good pharmacokinetic properties, including high oral bioavailability, moderate tissue distribution and long half-life, supporting once-daily dosing. Its good safety profile (low toxicity, no weight gain, no hypoglycemia) makes it suitable for long-term treatment of type 2 diabetes [1]
5. The chemical structure of DBPR108 is a dipeptide derivative ((2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidone-1-yl-propylamino)acetyl]-4-fluoro-pyrrolidone-2-nitrile), which gives it high affinity for DPP-IV and good oral bioavailability [1] Pulugliptin is a small molecule drug. The INN prefix "-gliptin" in its name indicates that pulugliptin is a dipeptidyl aminopeptidase-IV inhibitor. Pulugliptin is being investigated in the clinical trial NCT07026968 (Study of pulugliptin tablets in combination with dapagliflozin tablets and metformin hydrochloride extended-release tablets for the treatment of type 2 diabetes). The monoisotopic molecular weight of pulugliptin is 324.2 Da. |
| Molecular Formula |
C16H25FN4O2
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| Molecular Weight |
324.39
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| Exact Mass |
324.196
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| Elemental Analysis |
C, 59.24; H, 7.77; F, 5.86; N, 17.27; O, 9.86
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| CAS # |
1186426-66-3
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| Related CAS # |
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| PubChem CID |
44201003
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| Appearance |
White to off-white solid powder
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| LogP |
1.096
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
23
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| Complexity |
508
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)(CC(=O)N1CCCC1)NCC(=O)N2C[C@H](C[C@H]2C#N)F
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| InChi Key |
VQKSCYBKUIDZEI-STQMWFEESA-N
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| InChi Code |
InChI=1S/C16H25FN4O2/c1-16(2,8-14(22)20-5-3-4-6-20)19-10-15(23)21-11-12(17)7-13(21)9-18/h12-13,19H,3-8,10-11H2,1-2H3/t12-,13-/m0/s1
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| Chemical Name |
(2S,4S)-4-fluoro-1-[2-[(2-methyl-4-oxo-4-pyrrolidin-1-ylbutan-2-yl)amino]acetyl]pyrrolidine-2-carbonitrile
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| Synonyms |
(2S,4S)-4-fluoro-1-[2-[(2-methyl-4-oxo-4-pyrrolidin-1-ylbutan-2-yl)amino]acetyl]pyrrolidine-2-carbonitrile; (2S,4S)-4-fluoro-1-(2-((2-methyl-4-oxo-4-pyrrolidin-1-ylbutan-2-yl)amino)acetyl)pyrrolidine-2-carbonitrile; RefChem:131050; Prusogliptin; DBPR-108; DBPR108; DBPR 108 |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.71 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 25.0 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: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0827 mL | 15.4135 mL | 30.8271 mL | |
| 5 mM | 0.6165 mL | 3.0827 mL | 6.1654 mL | |
| 10 mM | 0.3083 mL | 1.5414 mL | 3.0827 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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