| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Gemigliptin targets dipeptidyl peptidase-4 (DPP-4), a serine exopeptidase that cleaves N-terminal dipeptides from proteins, including the incretin hormones GLP-1 and GIP. By inhibiting DPP-4, Gemigliptin prevents the rapid degradation of these incretins, thereby increasing their half-life and potentiating their effects. The compound is a highly selective, reversible, and competitive inhibitor of DPP-4, with an IC50 of 10.3 nM and a KD of 7.25 nM. This high potency and selectivity are important for minimizing off-target effects and for achieving effective glycemic control. By prolonging the activity of GLP-1 and GIP, Gemigliptin enhances glucose-dependent insulin secretion from pancreatic β-cells and suppresses glucagon release from α-cells. These effects lead to improved glycemic control, particularly in the postprandial state. In addition to its effects on glucose, DPP-4 inhibition may also have other beneficial effects, such as improving β-cell function and reducing inflammation. Gemigliptin's strong anti-glycosylation properties may also contribute to its overall therapeutic benefits. The compound's target, DPP-4, is a well-validated therapeutic target for type 2 diabetes, and its inhibition provides a safe and effective approach to managing blood glucose levels.
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| ln Vitro |
Gigliptin has an IC50 of 11.69 mM and suppresses the production of AGE-BSA in a dose-dependent manner[1]. With an IC50 of 1.39 mM, gigliptin dose-dependently inhibits the cross-linking of preformed AGE-BSA with rat tail tendon collagen[1]. Gigliptin's Ki is 7.25 nM, making it a competitive inhibitor[2].
Gemigliptin demonstrates potent in vitro activity as a DPP-4 inhibitor. It has an IC50 of 10.3 nM for human recombinant DPP-4 and a KD of 7.25 nM, indicating high potency and strong binding affinity. The compound is a highly selective, reversible, and competitive inhibitor, meaning it binds to the active site of DPP-4 in a reversible manner, competing with the natural substrates. This reversible binding allows for tight control of DPP-4 inhibition. In addition to its DPP-4 inhibitory activity, Gemigliptin has strong anti-glycosylation properties, which are important for preventing the formation of advanced glycation end-products (AGEs) that contribute to diabetic complications. These in vitro findings establish Gemigliptin as a potent and selective DPP-4 inhibitor with additional beneficial properties for the treatment of diabetes and its complications. |
| ln Vivo |
AGE production and AGE cross-linking are inhibited in vivo by gemigliptin (100 mg/kg; ig; daily; for 12 weeks) [1]. In rats, dogs, and monkeys, gigliptin suppresses plasma DPP-4 activity in a dose-dependent manner [2].
Gemigliptin demonstrates significant in vivo activity, primarily by lowering blood glucose levels through the inhibition of DPP-4 and the prolongation of incretin activity. The compound is approved in South Korea for the treatment of type 2 diabetes mellitus, confirming its clinical efficacy and safety. In preclinical studies, Gemigliptin has been shown to improve glycemic control in animal models of diabetes. Its strong anti-glycosylation properties suggest that it may also prevent diabetic complications such as nephropathy, neuropathy, and retinopathy. Further clinical studies have likely evaluated its long-term efficacy and safety in patients with type 2 diabetes. |
| Enzyme Assay |
Gemigliptin's in vitro enzyme activity is typically assessed using a DPP-4 enzyme assay. In a typical protocol, recombinant human DPP-4 is incubated with a fluorogenic substrate (e.g., Gly-Pro-AMC) and varying concentrations of Gemigliptin. The enzyme cleaves the substrate, releasing a fluorescent product (AMC), which is measured fluorometrically. The inhibition of enzyme activity by Gemigliptin is used to calculate the IC50 and Ki values. For Gemigliptin, this method has been used to determine its IC50 of 10.3 nM and its KD of 7.25 nM. These assays are crucial for characterizing the compound's inhibitory potency and binding kinetics.
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| Cell Assay |
Gemigliptin's in vitro cellular activity is typically assessed by measuring its effects on DPP-4 activity in cell-based systems or by evaluating its effects on incretin levels. In a typical assay, cells or plasma samples are incubated with a DPP-4 substrate, and the inhibition of substrate cleavage by Gemigliptin is measured. Alternatively, the compound's ability to increase GLP-1 or GIP levels in cell culture or plasma can be measured by ELISA. These cellular assays provide functional evidence for Gemigliptin's activity in a relevant biological context.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/KsJ-db/db mice (7 weeks old) [1]
Doses: 100 mg/kg Route of Administration: po (oral gavage) every day for 12 weeks Experimental Results: Circulating AGE levels in serum were Dramatically diminished by 44.5 %. Gemigliptin's in vivo activity is typically assessed in animal models of diabetes, such as db/db mice or Zucker diabetic fatty rats. In a typical study, animals are administered Gemigliptin orally, and blood glucose levels are measured at various time points. The compound's ability to lower blood glucose and improve glucose tolerance is assessed. Additionally, the effects of Gemigliptin on DPP-4 activity in plasma and on incretin levels are measured. These in vivo models are essential for demonstrating the compound's efficacy and for understanding its mechanism of action in a whole-organism context. |
| ADME/Pharmacokinetics |
Gemigliptin is characterized as being orally active. While specific PK parameters are not detailed in the provided references, its approval for clinical use confirms that it has a favorable PK profile in humans. Gemigliptin has a molecular weight of 489.36 and is soluble in DMSO. Further details on its PK properties can be found in the clinical literature.
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| Toxicity/Toxicokinetics |
Gemigliptin has been approved in South Korea for the treatment of type 2 diabetes mellitus, indicating that it has undergone rigorous toxicological testing and has an acceptable safety profile. The most common side effects associated with DPP-4 inhibitors are generally mild and include nasopharyngitis, headache, and gastrointestinal symptoms. Comprehensive toxicological assessments have been conducted to support its clinical development.
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| References |
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| Additional Infomation |
Gemigliptin is an organic nitrogen and organic oxygen compound whose function is related to β-amino acids. Gemigliptin is currently under investigation for the treatment of type 2 diabetes. It has also been used to treat cancer and adverse reactions to cisplatin. Gemigliptin is an orally bioavailable serine protease dipeptidyl peptidase-4 (DPP-4) inhibitor with hypoglycemic and potential renal protective effects. After administration, Gemigliptin binds to DPP-4, inhibiting the breakdown of incretin hormones—glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). This prolongs the activity of incretins, increases postprandial insulin secretion from pancreatic β-cells, reduces glucagon secretion, delays gastric emptying, and lowers blood glucose levels. Furthermore, Gemigliptin may exert its renal protective effect by enhancing GLP-1 signaling, potentially preventing apoptosis and acute kidney injury induced by nephrotoxic drugs, and may prevent diabetic nephropathy.
Gemigliptin is also known as LC15-0444. It is a highly selective, reversible, and competitive inhibitor of dipeptidyl peptidase-4 (DPP-4). Gemigliptin has an IC50 of 10.3 nM for human recombinant DPP-4 and a KD of 7.25 nM. It has strong anti-glycosylation properties and is used for the research of diabetic complications. Gemigliptin is approved in South Korea for the treatment of type 2 diabetes mellitus. The compound has a molecular formula of C18H19F8N5O2 and a molecular weight of 489.36. |
| Molecular Formula |
C18H19N5O2F8
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|---|---|
| Molecular Weight |
489.36296
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| Exact Mass |
489.141
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| Elemental Analysis |
C, 44.18; H, 3.91; F, 31.06; N, 14.31; O, 6.54
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| CAS # |
911637-19-9
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| Related CAS # |
Gemigliptin tartrate;1374639-74-3
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| PubChem CID |
11953153
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| Appearance |
White to orange solid powder
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| LogP |
2.95
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
746
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CC(CN(C1=O)C[C@H](CC(=O)N2CCC3=C(C2)N=C(N=C3C(F)(F)F)C(F)(F)F)N)(F)F
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| InChi Key |
ZWPRRQZNBDYKLH-VIFPVBQESA-N
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| InChi Code |
InChI=1S/C18H19F8N5O2/c19-16(20)3-1-12(32)31(8-16)6-9(27)5-13(33)30-4-2-10-11(7-30)28-15(18(24,25)26)29-14(10)17(21,22)23/h9H,1-8,27H2/t9-/m0/s1
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| Chemical Name |
1-[(2S)-2-amino-4-[2,4-bis(trifluoromethyl)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-7-yl]-4-oxobutyl]-5,5-difluoropiperidin-2-one
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| Synonyms |
Gemigliptin; LC 15-0444; LC-15-0444; LC150444; 911637-19-9; Gemigliptina; Gemigliptine; 5DHU18M5D6; LC15-0444; LC-150444; LC 150444; Gemigliptina; Gemigliptine; Gemigliptinum
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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 : ~50 mg/mL (~102.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.11 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 (5.11 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0435 mL | 10.2174 mL | 20.4349 mL | |
| 5 mM | 0.4087 mL | 2.0435 mL | 4.0870 mL | |
| 10 mM | 0.2043 mL | 1.0217 mL | 2.0435 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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