| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
Cofrogliptin targets DPP-4, an enzyme that degrades incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By inhibiting DPP-4, the compound increases the levels of active GLP-1 and GIP, which are released in response to food intake. These hormones enhance insulin secretion and suppress glucagon release in a glucose-dependent manner, leading to improved glycemic control.
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| ln Vitro |
Cofrogliptin (HSK7653) (compound 2) exhibits DPP-4 inhibitory action, with an IC50 of 4.18 nM[2].
In vitro, Cofrogliptin exhibits potent DPP-4 inhibitory activity with an IC50 of 4.18 nM. This demonstrates its high potency in inhibiting the enzymatic activity of DPP-4. Specific cellular assay data are not detailed in the available sources. |
| ln Vivo |
Cofrogliptin (HSK7653) (Compound 2) (IV: 0.5 mg/kg; PO: 2 mg/kg) demonstrates an unusually long half-life and a modest rate of reduction in drug concentration after oral administration. Colagliptin (Compound 2) (single dosage, oral, 3 mg/kg, 10 mg/kg, 30 mg/kg) has prolonged half-life, high oral exposure, venous clearance and hepatic microsomal clearance after intravenous injection Low. Cofrogliptin (Compound 2) (single dose, oral, 10 mg/kg) displayed extended DPP-4 inhibition in ob/ob mice and lowered HbA1c levels at dosages of 3 and 10 mg/kg. Cofrogliptin (compound 2) (single dose, oral, 10 mg/kg) also has significant potential for biweekly treatment of T2DM in rhesus monkeys [2]. ICR mouse pharmacokinetic parameters [2] IV (dose: 0.5 mg/kg) PO (dose: 2 mg/kg) CI (mL/min/kg) Vdss (L/kg) t1/2 (h) Cmax (ng/ mL) t1/2(h) AUC0-t(ng·h/mL) F% Ologliptin 7.39±2.1 1.65±0.27 3.05±0.6 798±122 4.65±1.4 4095±552 95.0±29 Kaog Gliptin (compound 2) 2.57±0.09 3.30±0.33 25.6±9.6 352±20 29.9±3.2 7898±873 62.2±6.9
In vivo, Cofrogliptin has demonstrated long-lasting hypoglycemic effects in preclinical models. In clinical trials, it provided glycemic control over 52 weeks and was generally well tolerated in patients with type 2 diabetes. It has an unusually long half-life, supporting once-weekly dosing. |
| Enzyme Assay |
A cell-free assay for Cofrogliptin involves measuring its inhibition of DPP-4 enzymatic activity. Recombinant DPP-4 is incubated with a chromogenic or fluorogenic substrate in the presence of varying concentrations of the compound. The rate of substrate cleavage is measured, and the IC50 is calculated. For Cofrogliptin, the IC50 is 4.18 nM.
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| Cell Assay |
Cellular assays for Cofrogliptin would typically involve measuring its effects on GLP-1 degradation in cell culture or in plasma. Cells or plasma are treated with the compound, and the stability of GLP-1 is assessed. The compound's ability to increase active GLP-1 levels confirms its DPP-4 inhibitory activity.
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| Animal Protocol |
Animal/Disease Models: ob/ob mice[2]
Doses: 3 mg/kg, 10 mg/kg, 30 mg/kg. Route of Administration: single dose, oral administration, 3 mg/kg, 10 mg/kg, 30 mg/kg. Experimental Results: It demonstrated strong inhibitory ability on plasma DPP-4 in a dose-dependent manner. Animal/Disease Models: Rhesus monkey[2] Doses: 10 mg/kg Route of Administration: Single oral administration, 10 mg/kg Experimental Results:It has more than 80% plasma DPP-4 inhibition ability, which lasts for at least 12 days. The plasma DPP-4 inhibition rates at the second and third weeks after administration were 76.16% and 43.41% respectively. In vivo animal experiments for Cofrogliptin have been conducted in models of type 2 diabetes. The compound's ability to lower blood glucose and improve glycemic control has been demonstrated. Specific protocols and data are not detailed in the available sources. |
| ADME/Pharmacokinetics |
Cofrogliptin is an orally active compound with an unusually long half-life. In pharmacokinetic studies, it was administered intravenously at 0.5 mg/kg and orally at 2 mg/kg. It has a modest rate of reduction in drug concentration after oral administration, supporting long-acting efficacy.
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| Toxicity/Toxicokinetics |
Toxicity data for Cofrogliptin indicate that it was generally well tolerated in clinical trials. Specific adverse effects are not detailed in the available sources. As an investigational drug, its full safety profile is still being established.
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| References | |
| Additional Infomation |
Cofrogliptin (CAS: 1844874-26-5) is a potent, orally active, long-acting DPP-4 inhibitor. It is also known as HSK7653. The compound has an IC50 of 4.18 nM and has demonstrated glycemic control in patients with type 2 diabetes. It is not an approved drug and is strictly for research purposes.
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| Molecular Formula |
C18H19F5N4O3S
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|---|---|
| Molecular Weight |
466.43
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| Exact Mass |
466.109
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| CAS # |
1844874-26-5
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| PubChem CID |
118613788
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| Appearance |
White to off-white solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
766
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C([C@@H]1[C@@H](C[C@@H]([C@H](O1)C1C=C(C=CC=1F)F)N)N1CC2C(C1)=NN(S(=O)(C)=O)C=2)(F)(F)F
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| InChi Key |
GUBOXFWNNXSQNH-SVGFKBNWSA-N
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| InChi Code |
InChI=1S/C18H19F5N4O3S/c1-31(28,29)27-7-9-6-26(8-14(9)25-27)15-5-13(24)16(30-17(15)18(21,22)23)11-4-10(19)2-3-12(11)20/h2-4,7,13,15-17H,5-6,8,24H2,1H3/t13-,15+,16+,17-/m0/s1
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| Chemical Name |
(2R,3S,5R,6S)-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-6-(trifluoromethyl)oxan-3-amine
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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 : ~100 mg/mL (~214.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.68 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 12.5 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. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.68 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 12.5 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 | 2.1439 mL | 10.7197 mL | 21.4394 mL | |
| 5 mM | 0.4288 mL | 2.1439 mL | 4.2879 mL | |
| 10 mM | 0.2144 mL | 1.0720 mL | 2.1439 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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