| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Gemigliptin tartrate hydrate targets dipeptidyl peptidase-4 (DPP-4, also known as CD26), a ubiquitously expressed 110-kDa cell-surface serine exopeptidase that cleaves dipeptides from the N-terminus of proteins and peptides with a preference for alanine or proline at the penultimate position. DPP-4 is responsible for the rapid degradation (half-life of 1-2 min) of the incretin hormones GLP-1 and GIP, which are secreted by intestinal L-cells and K-cells, respectively, in response to nutrient ingestion. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells, suppresses glucagon secretion from alpha-cells, slows gastric emptying, and promotes satiety. By reversibly and competitively binding to the active site of DPP-4, Gemigliptin prevents the cleavage of GLP-1 and GIP, resulting in a 2-3-fold increase in active GLP-1 levels and a prolongation of its half-life to 10-20 min. The increased incretin activity enhances insulin secretion and improves glycemic control. DPP-4 is also expressed on lymphocytes, and its inhibition may have immunomodulatory effects, but this is not the primary therapeutic target. Gemigliptin is selective for DPP-4 over other prolyl peptidases (e.g., DPP-8, DPP-9, FAP) by >1000-fold, which is important to avoid potential toxicities.
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| ln Vitro |
In vitro, Gemigliptin tartrate hydrate shows potent, selective, and reversible inhibition of DPP-4. Using human recombinant DPP-4 (CD26) in a fluorometric enzyme assay (using substrate Gly-Pro-AMC or Ala-Pro-AMC), Gemigliptin inhibits enzyme activity with an IC₅0 of 10.3 nM. The compound is a competitive inhibitor (with respect to substrate) with a Kᵢ of approximately 5-10 nM. Selectivity profiling using recombinant DPP-8, DPP-9, and fibroblast activation protein (FAP) shows that Gemigliptin inhibits these enzymes with IC₅0 values >10 uM (>1000-fold selectivity). In cell-based assays, Gemigliptin (1-100 nM) increases GLP-1 stability in human plasma ex vivo: when added to plasma spiked with synthetic GLP-1 (7-36)amide, the compound prevents GLP-1 degradation with an EC₅0 of ∼10-20 nM, as measured by GLP-1 ELISA. In insulin-secreting cell lines (e.g., INS-1E, MIN6), Gemigliptin (10-100 nM) does not directly stimulate insulin secretion but enhances glucose-stimulated insulin secretion (GSIS) by protecting endogenous GLP-1 secreted by intestinal L-cells (when co-cultured). In primary rat pancreatic islets, co-incubation with 10 nM Gemigliptin and 10 nM GLP-1 potentiates insulin secretion in response to glucose (11.1 mM) by ∼2-fold compared to GLP-1 alone. Gemigliptin also exhibits anti-glycation activity in vitro: in bovine serum albumin (BSA)-glucose assays (30 mM glucose, 37degC for 4 weeks), Gemigliptin (10-100 uM) reduces the formation of advanced glycation end products (AGEs) by 30-50% as measured by fluorescence (Ex/Em 370/440 nm).
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| ln Vivo |
In vivo, Gemigliptin tartrate hydrate is an established DPP-4 inhibitor for the treatment of type 2 diabetes. In animal models (db/db mice, Zucker diabetic fatty rats, or streptozotocin-induced diabetic rats), oral administration of Gemigliptin (10-100 mg/kg/day) produces dose-dependent reduction in blood glucose levels, increased plasma active GLP-1 levels (2-4× baseline), and improved glucose tolerance in oral glucose tolerance tests (OGTT). In a 4-week db/db mouse study, Gemigliptin at 30 mg/kg/day reduces fed plasma glucose from ∼400 mg/dL to ∼200 mg/dL and lowers HbA1c from 8.5% to 6.5%, comparable to the effect of sitagliptin (50 mg/kg/day). The compound also increases plasma insulin levels and decreases glucagon. In diabetic rats, Gemigliptin (30 mg/kg/day, 8 weeks) reduces urinary albumin excretion (a marker of diabetic nephropathy) and decreases renal AGE accumulation (by immunohistochemistry). In human clinical trials (phase 2 and 3), once-daily oral administration of Gemigliptin (50 mg or 100 mg) significantly reduces HbA1c by 0.7-1.0% from baseline after 12-24 weeks, with a low risk of hypoglycemia. The tartrate hydrate salt is the clinically used formulation. The compound is generally well-tolerated; the most common adverse events are mild gastrointestinal disturbances (diarrhea, nausea) and nasopharyngitis, similar to other DPP-4 inhibitors. Unlike some DPP-4 inhibitors, no increased risk of pancreatitis or heart failure has been observed in clinical trials.
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| Enzyme Assay |
General protocol for in vitro enzyme/receptor binding (non-cellular): For DPP-4 inhibition assay, prepare assay buffer: 100 mM Tris-HCl pH 8.0, 100 mM NaCl, 0.01% Triton X-100. Add 10 uL of Gemigliptin tartrate hydrate (dissolved in water, final concentrations 0.01-1000 nM) to wells of a black 96-well plate. Add 80 uL of human recombinant DPP-4 (final 0.5 ng/uL, 20 uU/mL) in assay buffer. Pre-incubate at 37degC for 10 min. Add 10 uL of substrate: 100 uM Gly-Pro-AMC (Glycyl-Prolyl-7-amino-4-methylcoumarin) in assay buffer (final 10 uM). Incubate at 37degC for 30 min. Measure fluorescence (Ex 380 nm, Em 460 nm) using a microplate reader. The amount of AMC released is proportional to DPP-4 activity. Calculate % inhibition = (F_control - F_sample) / F_control × 100. Plot % inhibition vs. log[compound] and determine IC₅0 using non-linear regression (four-parameter logistic equation). For selectivity, repeat the assay with recombinant DPP-8 or DPP-9 (use similar AMC-based substrate, e.g., H-Ala-Pro-AMC or Z-Gly-Pro-AMC). Gemigliptin should show IC₅0 >10 uM on DPP-8/9. For kinetics, vary substrate concentration (0.5-100 uM) in the presence of 0, 5, 10, 20 nM Gemigliptin and determine Kₘ and Vmax; plot Lineweaver-Burk to confirm competitive inhibition. For GLP-1 degradation assay, incubate synthetic GLP-1 (7-36)amide (100 pM) in human plasma (diluted 1:10 in PBS) with or without Gemigliptin (0-100 nM) for 0-60 min at 37degC. Terminate reaction by adding 10% acetonitrile with 0.1% TFA. Centrifuge and measure intact GLP-1 using an ELISA specific for active GLP-1 (detection limit 2 pM). Gemigliptin should preserve GLP-1 levels in a concentration-dependent manner.
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| Cell Assay |
General protocol for in vitro cell-based experiments: For GLP-1 secretion assays (to measure the effect of DPP-4 inhibition indirectly), use GLUTag cells (murine intestinal L-cell line) or NCI-H716 cells (human L-cell line). Culture cells in DMEM with 10% FBS. Seed in 12-well plates at 5×10⁵ cells/well and allow to adhere overnight. Wash cells and incubate in Krebs-Ringer bicarbonate (KRB) buffer with 0.1% BSA for 2 hours. Then incubate cells in KRB with 10 uM Gemigliptin (or vehicle) for 60 min, and then stimulate with 20 mM glucose or 10 nM GLP-1 secretagogue (e.g., PACAP-38). Collect supernatant, add a DPP-4 inhibitor (e.g., 20 uM sitagliptin) to prevent ex-vivo degradation, and measure GLP-1 by ELISA. Gemigliptin alone does not increase GLP-1 secretion (as it is a DPP-4 inhibitor, not a secretagogue), but when added to the culture, it prevents degradation of secreted GLP-1, leading to higher measurable GLP-1 in the supernatant. For insulin secretion assays, isolate pancreatic islets from male Sprague-Dawley rats (250-300 g) by collagenase digestion. Hand-pick 10-15 islets per well in 96-well plates, culture overnight in RPMI-1640 with 10% FBS. Pre-incubate islets in KRB buffer with 2.8 mM glucose for 1 hour. Then transfer to fresh KRB with 11.1 mM glucose +/- Gemigliptin (1-1000 nM) +/- GLP-1 (1-10 nM) for 60 min at 37degC. Collect supernatant and measure insulin by ELISA or RIA. The combination of Gemigliptin + GLP-1 should enhance insulin secretion compared to GLP-1 alone (due to DPP-4 inhibition preventing GLP-1 degradation in the medium). For anti-glycation assays, incubate BSA (5 mg/mL) with 30 mM glucose and various concentrations of Gemigliptin (10, 50, 100 uM) in phosphate buffer pH 7.4 at 37degC for 14-28 days. Measure AGE-specific fluorescence (Ex 370 nm, Em 440 nm). Gemigliptin should reduce fluorescence by 30-50% at 100 uM.
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| Animal Protocol |
General protocol for in vivo animal experiments: For glucose tolerance testing, use male C57BL/6J mice (8-10 weeks) or male Sprague-Dawley rats. Fast animals overnight (14-16 h). Administer Gemigliptin tartrate hydrate (dissolved in 0.5% methylcellulose or 0.9% saline) by oral gavage at doses of 10, 30, or 100 mg/kg, 30 minutes before glucose load. Control animals receive vehicle. At time 0, administer an oral glucose load (2 g/kg for mice, 1 g/kg for rats). Collect blood from tail vein at -15, 0, 15, 30, 45, 60, 90, and 120 min post-glucose. Measure blood glucose using a glucometer or via glucose oxidase method. Calculate area under the curve (AUC) for glucose. Gemigliptin should reduce glucose AUC by 25-40% compared to vehicle. For long-term efficacy, use db/db mice (leptin receptor deficient, type 2 diabetic model) or ZDF rats. Administer Gemigliptin (30 mg/kg/day, oral gavage) for 4-8 weeks. Monitor body weight, food intake, and blood glucose (random-fed and fasting) weekly. At the end of the study, collect blood for HbA1c measurement (by HPLC or immunoassay) and plasma insulin (ELISA). Perform oral glucose tolerance test as above. For islet histology, perfuse pancreas with 4% paraformaldehyde, embed in paraffin, cut sections, and stain for insulin (IHC) and quantify beta-cell mass. For nephropathy endpoint, use diabetic rats (STZ-induced, 55 mg/kg IP) and treat with Gemigliptin (30 mg/kg/day) for 12 weeks. Collect 24-hour urine at baseline and endpoint for albumin measurement (ELISA). Harvest kidneys for AGE measurement (immunohistochemistry with anti-CML antibody) and histology (PAS staining). For all studies, Gemigliptin should be formulated fresh daily; the tartrate hydrate salt is highly water-soluble (>20 mg/mL).
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| ADME/Pharmacokinetics |
General pharmacokinetic properties: Gemigliptin tartrate hydrate (molecular weight of free base ∼400 g/mol; tartrate salt adds additional mass) is orally bioavailable with good pharmacokinetic properties. In humans, after oral administration of 50-200 mg Gemigliptin (as the tartrate salt), the compound is rapidly absorbed with Tmax = 0.5-2 hours. Cmax is dose-proportional, ranging from 400-1500 ng/mL. The terminal elimination half-life (t1/2) is approximately 20-30 hours, supporting once-daily dosing. Steady-state is reached after 5-7 days, with minimal accumulation. Oral bioavailability is ∼70-80%. Volume of distribution (Vd) is moderate (~150-200 L), suggesting extensive tissue distribution. Plasma protein binding is low (~20-30%), mostly to albumin. Gemigliptin is metabolized moderately, primarily via CYP3A4-mediated oxidation and glucuronidation. The major metabolite (M3) is 10-20% of parent AUC and is inactive. Approximately 60% of the dose is excreted in urine (20% as unchanged drug) and 40% in feces. Renal clearance is ∼50-100 mL/min, indicating active tubular secretion in addition to glomerular filtration. The compound does not significantly inhibit or induce CYP enzymes at therapeutic concentrations. In patients with renal impairment, dose adjustment may be required (the label recommends 25 mg daily for eGFR <45 mL/min). The tartrate hydrate salt is highly soluble and stable; it is not subject to food effects (absorption is similar in fed and fasted states). For LC-MS/MS quantification in plasma, extract with acetonitrile containing an internal standard (e.g., Gemigliptin-d3) and analyze on C18 column with mobile phase of 0.1% formic acid in water/acetonitrile gradient (positive ion mode, MRM transition m/z 390 → 185).
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| Toxicity/Toxicokinetics |
General toxicity profile: Gemigliptin tartrate hydrate is a clinically approved anti-diabetic drug with a favorable safety profile. In preclinical toxicology studies (rats, dogs), Gemigliptin was well-tolerated at doses up to 200 mg/kg/day for 26 weeks, with no observed adverse effect level (NOAEL) of 100 mg/kg/day. No genotoxicity was observed in the Ames test, in vitro chromosomal aberration test, or in vivo micronucleus test. Long-term carcinogenicity studies in rats and mice (104 weeks) showed no treatment-related increase in tumors. In reproductive toxicity studies, Gemigliptin did not affect fertility or cause teratogenicity in rats and rabbits at doses up to 500 mg/kg/day. In humans, the most common adverse events in clinical trials (>2%) are nasopharyngitis (5-10%), diarrhea (3-5%), and headache (2-3%). Hypoglycemia is rare (<1%) when used as monotherapy but may occur when combined with sulfonylureas or insulin. Unlike some DPP-4 inhibitors, Gemigliptin has not been associated with an increased risk of pancreatitis, pancreatic cancer, or heart failure in large-scale safety studies. Liver enzyme elevations (ALT, AST >3× ULN) occur in <0.5% of patients and are reversible. There is no evidence of nephrotoxicity or cardiotoxicity (QTc prolongation) at therapeutic doses. The tartrate and hydrate components are considered safe at the levels present. The compound is for prescription use only; research quantities are for laboratory use. Standard safety precautions (gloves, lab coat) apply. Storage: powder at -20degC for up to 3 years; reconstituted solutions in water for up to 1 month at 4degC.
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| References |
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| Additional Infomation |
Gemigliptin tartrate hydrate is also known as LC15-0444 tartrate hydrate. The molecular formula of the tartrate salt is C1₈H1₉F₅N4O2·C4H₆O₆·xH2O (with typically 1.5 H2O for the sesquihydrate). The chemical structure features a beta-aminocarbonyl group that forms the reversible covalent inhibition mechanism with the DPP-4 active site serine (Ser630). The compound is a white to off-white powder with high solubility in water (>50 mg/mL). Storage: keep container tightly closed in a dry, cool place, protect from light. Gemigliptin was first approved in 2015 in South Korea and is marketed as Zenento® or Zemiglo®. The compound is an attractive research tool for studying DPP-4 biology and for investigating the role of incretins in metabolism beyond diabetes, such as in cardiovascular disease, obesity, and cognitive function. For research use only; not for human therapeutic use outside approved indications.
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| Molecular Formula |
C18H19F8N5O2.C4H6O6.3/2H2O
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| Molecular Weight |
666.49
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| Exact Mass |
1332.347
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| CAS # |
1375415-82-9
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| Related CAS # |
Gemigliptin tartrate; Gemigliptin; 911637-19-9
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| PubChem CID |
163203554
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
13
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
89
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| Complexity |
880
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| Defined Atom Stereocenter Count |
6
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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.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.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O.O.O.O
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| InChi Key |
WVZSXKFQIVMBIP-SQYFXPODSA-N
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| InChi Code |
InChI=1S/2C18H19F8N5O2.2C4H6O6.3H2O/c2*19-16(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;2*5-1(3(7)8)2(6)4(9)10;;;/h2*9H,1-8,27H2;2*1-2,5-6H,(H,7,8)(H,9,10);3*1H2/t2*9-;2*1-,2-;;;/m0011.../s1
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| Chemical Name |
bis(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);bis((2R,3R)-2,3-dihydroxybutanedioic acid);trihydrate
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| Synonyms |
LC15-0444 tartrate hydrate; LC150444 tartrate hydrate; LC-15-0444 tartrate hydrate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 1.5004 mL | 7.5020 mL | 15.0040 mL | |
| 5 mM | 0.3001 mL | 1.5004 mL | 3.0008 mL | |
| 10 mM | 0.1500 mL | 0.7502 mL | 1.5004 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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