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500mg | ||
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Vildagliptin (LAF237 dihydrate; NVP-LAF 237 dihydrate) is a selective dipeptidyl peptidase 4 (DPP4) inhibitor with an IC50 of 3.5 nM in human Caco-2 cells. It delays the degradation of glucagon-like peptide-1 (GLP-1). Vildagliptin dihydrate possesses excellent oral bioavailability and potent antihyperglycemic activity.
Targets |
DPP-IV (IC50 = 3.5 nM)
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ln Vitro |
Vildagliptin inhibits apoptosis to increase β-cell survival. Additionally, vildagliptin stimulates cell division [2].
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ln Vivo |
Vildagliptin raises plasma active GLP-1 levels in the islets of db/db mice when administered orally once daily at a dose of 35 mg/kg [2]. Vildagliptin (10 µmol/kg; oral) in obese male Zucker rats dramatically lowers glucose excursions and increases insulin secretion [1].
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Enzyme Assay |
DPP-IV Inhibition Measurement ex Vivo.Rat, Human, Monkey Plasma Assays.[4]
Human, rat, or monkey plasma was used as the source of DPP-IV in the assay. The standard assay was modified from a previously published method. Five μL of plasma was added to 96-well flat-bottom microtiter plates, followed by the addition of 5 μL of 80 mM MgC12 in assay buffer (25 mM HEPES, 140 mM NaC1, 1% RIA-grade BSA, pH 7.8). After a 5-min preincubation at room temperature, the reaction was initiated by the addition of 10 μL of assay buffer containing 0.1 mM substrate (H-Gly-Pro-AMC; AMC is 7-amino-4-methylcoumarin). The plates were covered with aluminum foil (or kept in the dark) and incubated at room temperature for 20 min. After incubation, fluorescence was measured using a CytoFluor II fluorometer (excitation 380 nm/ emission 460 nm). Test compounds and solvent controls were added as 2 μL additions, and the assay buffer volume was reduced to 13 μL. A standard curve of free AMC was generated using 0−50 μM solutions of AMC. The curve generated, which was linear, was used for interpolation of substrate consumption (catalytic activity in nmoles substrate cleaved /min). DPP-II Inhibition Measurement in Vitro. [4] An extract of bovine kidney homogenate, partially purified by ion-exchange and adenosine deaminase chromatography, was used as the source of DPP-II in the assay. The standard assay was modified from a previously published method. 47 Twenty micrograms of DPP-II-containing fraction diluted to a final volume of 60 μL in assay buffer (0.2 M Borate, 0.05 M Citrate, pH 5.3) was added to 96-well flat-bottom microtiter plates, followed by the addition of 10 μL of 10 mM o-phenanthroline (to inhibit aminopeptidase activity) and 20 μL of 5 mM substrate (H-Lys-Ala-AMC; AMC is 7-amino-4-methylcoumarin). The plates were incubated at 37 °C for 30 min. After incubation, fluorescence was measured using a CytoFluor II fluorometer (excitation 380 nm/ emission 460 nm). Test compounds and solvent controls were added as 20 μL additions, and assay buffer volume is reduced to 50 μL. A standard curve of AMC was generated using 0 to 100 μM of AMC. The curve generated, which was linear, was used for interpolation of catalytic activity (in nmoles substrate cleaved/min). Vildagliptin (LAF-237; NVP-LAF 237) has an IC50 of 2.3 nM, which inhibits DPP-4. Figure 2 represents vildagliptin, an N-substituted glycyl-2-cyanopyrrolidine. With an inhibitory concentration (IC50) of approximately 2–3 nmol/L, it is a strong, reversible, and competitive inhibitor of DPP-4 in both humans and rodents in vitro. Crucially, vildagliptin exhibits high specificity inhibition of DPP-4 in comparison to other analogous peptidases, wherein its IC50 surpasses 200 mol/L. |
Cell Assay |
In Vitro Studies.DPP-IV Inhibition Measurement in Vitro: Caco-2 Assay. [4]
An extract from human colonic carcinoma cells (Caco-2; American Type Culture Collection; ATCC HTB 37) was used as the source of DPP-IV in the assay. The cells were differentiated to induce DPP-IV expression as described by previously. Cell extract was prepared from cells solubilized in lysis buffer (10 mM Tris-HC1, 0.15 M NaC1, 0.04 T.I.U. (trypsin inhibitor unit) aprotinin, 0.5% nonidet-P40, pH 8.0) then centrifuged at 35 000g for 30 min at 4 °C to remove cell debris. The assay was conducted by adding 20 μg of solubilized Caco-2 protein, diluted to a final volume of 125 μL in assay buffer (25 mM Tris-HC1 pH 7.4, 140 mM NaC1, 10 mM KC1, 1% bovine serum albumin) to 96-well flat-bottom microtiter plates. The reaction was initiated by adding 25 μL of 1 mM substrate (H-Ala-Pro-pNA; pNA is p-nitroaniline). The reaction was run at room temperature for 10 min, and then 19 μL of 25% glacial acetic acid was added to stop the reaction. Fluorescence was measured using a CytoFluor II fluorometer (excitation 380 nm/ emission 460 nm). Test compounds and solvent controls were added as 30 μL additions, and the assay buffer volume was reduced to 95 μL. A standard curve of free p-nitroaniline was generated using 0−100 μM pNA in assay buffer. The curve generated, which was linear, was used for interpolation of substrate consumption (catalytic activity in nmoles substrate cleaved /min). Post-Proline Cleaving Enzyme (PPCE) Inhibition Measurement in Vitro. [4] A cytosolic extract of human erythrocytes, partially purified by ion-exchange chromatography, was used as the source of PPCE in the assay. The standard assay is modified from a previously published method. PPCE-containing fraction (350 ng protein) diluted to a final volume of 90 μL in assay buffer (20 mM NaPO4, 0.5 mM EDTA, 0.5 mM DTT, 1% BSA, pH 7.4) was added to 96-well flat-bottom microtiter plates, followed by the addition of 10 μL of 0.5 mM substrate (Z-Gly-Pro-AMC; AMC is 7-amino-4-methylcoumarin). The plates were incubated at room temperature for 30 min. After incubation, fluorescence was measured using a CytoFluor II fluorometer (excitation 380 nm/ emission 460 nm). Test compounds and solvent controls were added as 20 μL additions, and the assay buffer volume was reduced to 70 μL. A standard curve of free AMC was generated using 0 to 5 μM solutions of AMC. The curve generated, which was linear, was used for interpolation of catalytic activity (in nmoles substrate cleaved/min). |
Animal Protocol |
Animal/Disease Models: Male db/db mice (BKS) and wild-type mice [2]
Doses: 35 mg/kg Route of Administration: po (oral gavage); one time/day; for 6 weeks Experimental Results: Increased plasma active GLP-1 levels (22.63±1.19 vs. 11.69±0.44). Animal/Disease Models: Obese male Zucker rat [1] Doses: 10 µmol/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Oral Experimental Results:Dramatically diminished blood sugar fluctuations and stimulated insulin secretion. In Vivo Obese Male (fa/fa) Zucker Rat Studies.[1] Effect of Vildagliptin (NVP LAF 237; DSP7238; LAF237) (Vildagliptin (NVP LAF 237; DSP7238; LAF237) ) on DPP-IV Activity, Active GLP-1 Levels, and Glucose and Insulin Excursions. Studies were performed on obese male Zucker (fa/fa) rats (Charles River Labs, Cambridge, MA); controls (n = 9) and Vildagliptin (NVP LAF 237; DSP7238; LAF237) -treated (n = 9). These rats were purchased at 7 weeks of age, cannulated at 7.5 weeks, and studied beginning at around 11 weeks of age. In the morning of the oral glucose tolerance test (OGTT), the rats were “fasted” by removing food before the lights were turned on, after which they were transferred to the experiment room at 8:00 a.m.. Vildagliptin (NVP LAF 237; DSP7238; LAF237) was dissolved in vehicle solution (0.5% carboxymethylcellulose (CMC) and 0.2% Tween 80). The cannulas were connected to sampling tubing (PE-100, 0.034 in. i.d. × 0.06 in. o.d.), which were filled with saline. After 30−40 min cage acclimation, a 0.5 mL baseline blood sample was taken at t = −15 min, and the rats were then orally dosed with CMC or Vildagliptin (NVP LAF 237; DSP7238; LAF237) (10 μmol/kg), after which additional baseline blood samples were taken at t = −5, −2.5, and 0 min. The animals were then administered an oral glucose solution (10% glucose, 1 g/kg) immediately after t = 0‘. The rest of the samples were taken at 1, 3, 5, 10, 15, 20, 30, 45, 60, 75, and 90 min. Throughout the OGTT, an equal volume of donor blood was used to replace the blood withdrawn during sampling. Donor blood was obtained from donor rats through cardiac puncture. The collected blood samples (0.5 mL) were immediately transferred into chilled Eppendorf tubes containing 50 μL of EDTA: trasylol (25 mg/mL of 10 000 trasylol) and used for the measurement of glucose and insulin levels and DPP-IV activity. Larger blood samples (0.75 mL) were collected at t = −15, 0, 5, 10, 15, and 30 min for GLP-1 (7−36 amide) measurements. To these tubes, the DPP-IV inhibitor valine pyrrolidide was added to yield a final concentration in the blood of 1 μM. Technical difficulties with obtaining blood samples after minute 20 for one rat in both the CMC and Vildagliptin (NVP LAF 237; DSP7238; LAF237) groups resulted in the inability to calculate glucose and insulin AUC data for those rats, leading to AUC data with an n = 8/group. Measurement of plasma glucose was made using a modification of a Sigma Diagnostics glucose oxidase kit. DPP-IV activity was measured in plasma samples obtained at −5, 0, 20, 45, and 90 min DPP-IV activity as previously described in the above ex vivo rat plasma experimental. Plasma levels of GLP-1 (7−36 amide) were measured using the GLP-1 (active) Elisa Kit. In Vivo Cynomolgus Monkey PK/PD Studies Using 8c and Vildagliptin (NVP LAF 237; DSP7238; LAF237) . [1] Ketamine-anesthetized male healthy cynomolgus monkeys received either 8c (n = 2) or Vildagliptin (NVP LAF 237; DSP7238; LAF237) (n = 3) (dissolved in CMC/Tween-80) by oral gavage (1.007 μmol/kg), and by intravenous administration (0.399 μmol/kg) (dissolved in saline). For iv study, compound was administered (0.4 mL/kg over 1 min) in 0.9% saline as vehicle. Different monkeys were used for each dosage regimen. Basal blood samples were collected at −10 min and immediately prior to administration of compound. Blood samples were collected at 0.03, 0.08, 0.17, 0.25, 0.33, 0.42, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 7, 12, and 25 h postdose for both routes of administration. Blood was obtained into heparin-coated syringes, transferred to microcentrifuge tubes, and centrifuged to separate the plasma. The plasma was stored at −80 °C in fresh microcentrifuge tubes until assay. DPP-IV activity was measured in a similar manner was as previously described in the above ex vivo rat and human plasma experimentals. Plasma DPP-IV activities were calculated and expressed as ‘percent of baseline' to reduce variability due to individual differences in plasma enzyme activity. Area-under-curve (AUC) values for DPP-IV activity were calculated from time (hours after dose) vs effect (percent inhibition) curves from individual animals using the trapezoidal method. The ratio of dose-normalized effect AUC for oral/intravenous administration routes was taken as an estimate of effect bioavailability. Parent drug concentrations were determined using an HPLC/MS/MS method with a limit of quantification of 1 ng/mL. Pharmacokinetic parameters were calculated using noncompartment modeling, and the AUC was calculated using the linear trapezoidal method. Absolute oral bioavailability was calculated by (AUC0-∞po × 399)/(AUC0-∞iv × 1007). Vildagliptin was orally administered to db/db mice for 6 weeks, followed by evaluation of beta cell apoptosis by caspase3 activity and TUNEL staining method. Endoplasmic reticulum stress markers were determined with quantitative RT-PCR, immunohistochemistry and immunoblot analysis. Results: After 6 weeks of treatment, vildagliptin treatment increased plasma active GLP-1 levels (22.63±1.19 vs. 11.69±0.44, P<0.001), inhibited beta cell apoptosis as demonstrated by lower amounts of TUNEL staining nuclei (0.37±0.03 vs. 0.55±0.03, P<0.01) as well as decreased caspase3 activity (1.48±0.11 vs. 2.67±0.13, P<0.01) in islets of diabetic mice compared with untreated diabetic group. Further, vildagliptin treatment down-regulated several genes related to endoplasmic reticulum stress including TRIB3 (tribbles homolog 3) (15.9±0.4 vs. 33.3±1.7, ×10⁻³, P<0.001), ATF-4(activating transcription factor 4) (0.83±0.06 vs. 1.42±0.02, P<0.001) and CHOP(C/EBP homologous protein) (0.07±0.01 vs. 0.16±0.01, P<0.001). Conclusions: Vildagliptin promoted beta cell survival in db/db mice in association with down-regulating markers of endoplasmic reticulum stress including TRIB3, ATF-4 as well as CHOP.[5] |
ADME/Pharmacokinetics |
Absorption
In a fasting state, vildagliptin is rapidly absorbed following oral administration. Peak plasma concentrations are observed at 1.7 hours following administration. Plasma concentrations of vildagliptin increase in an approximately dose-proportional manner. Food delays Tmax to 2.5 hours and decreases Cmax by 19%, but has no effects on the overall exposure to the drug (AUC). Absolute bioavailability of vildagliptin is 85%. Route of Elimination Vildagliptin is eliminated via metabolism. Following oral administration, approximately 85% of the radiolabelled vildagliptin dose was excreted in urine and about 15% of the dose was recovered in feces. Of the recovered dose in urine, about 23% accounted for the unchanged parent compound. Volume of Distribution The mean volume of distribution of vildagliptin at steady-state after intravenous administration is 71 L, suggesting extravascular distribution. Clearance After intravenous administration to healthy subjects, the total plasma and renal clearance of vildagliptin were 41 and 13 L/h, respectively. Metabolism / Metabolites About 69% of orally administered vildagpliptin is eliminated via metabolism not mediated by cytochrome P450 enzymes. Based on the findings of a rat study, DPP-4 contributes partially to the hydrolysis of vildagliptin. Vildagliptin is metabolized to pharmacologically inactive cyano (57%) and amide (4%) hydrolysis products in the kidney. LAY 151 (M20.7) is a major inactive metabolite and a carboxylic acid that is formed via hydrolysis of the cyano moiety: it accounts for 57% of the dose. Other circulating metabolites reported are an N-glucuronide (M20.2), an N-amide hydrolysis product (M15.3), two oxidation products, M21.6 and M20.9. Biological Half-Life The mean elimination half-life following intravenous administration is approximately two hours. The elimination half-life after oral administration is approximately three hours. |
Toxicity/Toxicokinetics |
Protein Binding
The plasma protein binding of vildagliptin is 9.3%. Vildagliptin distributes equally between plasma and red blood cells. |
References |
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Additional Infomation |
Vildagliptin is an amino acid amide.
Vildagliptin (LAF237) is an orally active antihyperglycemic agent that selectively inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme. It is used to manage type II diabetes mellitus, where GLP-1 secretion and insulinotropic effects are impaired. By inhibiting DPP-4, vildagliptin prevents the degradation of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are incretin hormones that promote insulin secretion and regulate blood glucose levels. Elevated levels of GLP-1 and GIP consequently results in improved glycemic control. In clinical trials, vildagliptin has a relatively low risk of hypoglycemia. Oral vildagliptin was approved by the European Medicines Agency in 2008 for the treatment of type II diabetes mellitus in adults as monotherapy or in combination with [metformin], a sulfonylurea, or a thiazolidinedione in patients with inadequate glycemic control following monotherapy. It is marketed as Galvus. Vildagliptin is also available as Eucreas, a fixed-dose formulation with metformin for adults in who do not adequately glycemic control from monotherapy. Vildagliptin is currently under investigation in the US.
Vildagliptin is a cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Vildagliptin's cyano moiety undergoes hydrolysis and this inactive metabolite is excreted mainly via the urine. A pyrrolidine-carbonitrile derivative and potent inhibitor of DIPEPTIDYL PEPTIDASE 4 that is used in the treatment of TYPE 2 DIABETES MELLITUS. Drug Indication Vildagliptin is indicated in the treatment of type II diabetes mellitus in adults. As monotherapy, vildagliptin is indicated in adults inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance. It is also indicated as dual therapy in combination with metformin, a sulphonylurea, or a thiazolidinedione in adults patients with insufficient glycemic control despite maximal tolerated dose of monotherapy. Vildagliptin is also marketed in a combination product with [metformin] for the treatment of adults with type II diabetes mellitus who inadequately respond to either monotherapy of vildagliptin or metformin. This fixed-dose formulation can be used in combination with a sulphonylurea or insulin (i.e., triple therapy) as an adjunct to diet and exercise in adults who do not achieve adequate glycemic control with monotherapy or dual therapy. Vildagliptin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: as monotherapy in patients in whom metformin is inappropriate due to contraindications or intolerance. in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control (see sections 4. 4, 4. 5 and 5. 1 for available data on different combinations). Vildagliptin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: as monotherapy in patients in whom metformin is inappropriate due to contraindications or intolerance. in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. Pharmacodynamics Vildagliptin works to improve glycemic control in type II diabetes mellitus by enhancing the glucose sensitivity of beta-cells (β-cells) in pancreatic islets and promoting glucose-dependent insulin secretion. Increased GLP-1 levels leads to enhanced sensitivity of alpha cells to glucose, promoting glucagon secretion. Vildagliptin causes an increase in the insulin to glucagon ratio by increasing incretin hormone levels: this results in a decrease in fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. It also has no effects on insulin secretion or blood glucose levels in individuals with normal glycemic control. In clinical trials, treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta-cells, proinsulin to insulin ratio, and measures of beta-cell responsiveness from the frequently-sampled meal tolerance test. Vildagliptin has improves glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels. Mechanism of Action Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones that regulate blood glucose levels and maintain glucose homeostasis. It is estimated that the activity of GLP-1 and GIP contribute more than 70% to the insulin response to an oral glucose challenge. They stimulate insulin secretion in a glucose-dependent manner via G-protein-coupled GIP and GLP-1 receptor signalling. In addition to their effects on insulin secretion, GLP-1 is also involved in promoting islet neogenesis and differentiation, as well as attenuating pancreatic beta-cell apoptosis. Incretin hormones also exert extra-pancreatic effects, such as lipogenesis and myocardial function. In type II diabetes mellitus, GLP-1 secretion is impaired, and the insulinotropic effect of GIP is significantly diminished. Vildagliptin exerts its blood glucose-lowering effects by selectively inhibiting dipeptidyl peptidase-4 (DPP-4), an enzyme that rapidly truncates and inactivates GLP-1 and GIP upon their release from the intestinal cells. DPP-4 cleaves oligopeptides after the second amino acid from the N-terminal end. Inhibition of DPP-4 substantially prolongs the half-life of GLP-1 and GIP, increasing the levels of active circulating incretin hormones. The duration of DPP-4 inhibition by vildagliptin is dose-dependent. Vildagliptin reduces fasting and prandial glucose and HbA1c. It enhances the glucose sensitivity of alpha- and beta-cells and augments glucose-dependent insulin secretion. Fasting and postprandial glucose levels are decreased, and postprandial lipid and lipoprotein metabolism are also improved. |
Molecular Formula |
C17H27N3O3
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Molecular Weight |
321.41458439827
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Exact Mass |
339.215
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CAS # |
2133364-01-7
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Related CAS # |
Vildagliptin;274901-16-5;(2R)-Vildagliptin;1036959-27-9
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PubChem CID |
167996054
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Appearance |
Typically exists as solid at room temperature
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Hydrogen Bond Donor Count |
4
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Hydrogen Bond Acceptor Count |
6
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Rotatable Bond Count |
3
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Heavy Atom Count |
24
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Complexity |
523
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Defined Atom Stereocenter Count |
3
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SMILES |
N(C12CC3CC(CC(C3)(O)C1)C2)CC(N1CCC[C@H]1C#N)=O.O
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InChi Key |
MVOBUCAQTXEOGS-XQOPLDTQSA-N
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InChi Code |
InChI=1S/C17H25N3O2.2H2O/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16;;/h12-14,19,22H,1-8,10-11H2;2*1H2/t12-,13+,14-,16?,17?;;/m0../s1
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Chemical Name |
(2S)-1-[2-[[(5S,7R)-3-hydroxy-1-adamantyl]amino]acetyl]pyrrolidine-2-carbonitrile;dihydrate
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Synonyms |
LAF-237 dihydrate; Vildagliptin dihydrate; 2133364-01-7; (2S)-1-[2-[[(5S,7R)-3-hydroxy-1-adamantyl]amino]acetyl]pyrrolidine-2-carbonitrile;dihydrate NVPLAF 237 dihydrate; LAF 237 dihydrate NVP-LAF-237 dihydrate; LAF237 dihydrate; NVP-LAF 237 dihydrate
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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 | 3.1113 mL | 15.5565 mL | 31.1129 mL | |
5 mM | 0.6223 mL | 3.1113 mL | 6.2226 mL | |
10 mM | 0.3111 mL | 1.5556 mL | 3.1113 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04410341 | Recruiting | Drug: Vildagliptin 50 MG Drug: Escitalopram 20 mg |
Major Depressive Disorder | Sadat City University | May 1, 2020 | Phase 1 Phase 2 |
NCT05429554 | Recruiting | Drug: Vildagliptin | Type 2 Diabetes Mellitus | MTI University | June 2022 | |
NCT04761861 | Recruiting | Drug: Vildagliptin 50 MG Drug: Placebo |
Schizophrenia Dyslipidemias |
Sadat City University | February 16, 2021 | Phase 2 |
NCT03925701 | Recruiting | Drug: Vildagliptin Drug: vildagliptin\metformin |
dm | Sherief Abd-Elsalam | April 1, 2019 | Phase 3 |
NCT06068686 | Recruiting | Drug: Vildagliptin 50 MG Drug: Glimepiride 3 Mg Oral Tablet |
Type 2 Diabetes | Damanhour University | October 1, 2022 | Not Applicable |