DPP-IV (IC50 = 3.5 nM)
Vildagliptin (NVP LAF 237; DSP7238; LAF237) is a potent, selective inhibitor of dipeptidyl peptidase-4 (DPP-4), with an IC50 of 1.6 nM for human recombinant DPP-4 in cell-free enzyme assays and a Ki of 0.4 nM (competitive inhibition) [1]
- It shows no significant inhibition of other dipeptidyl peptidases (DPP-8, DPP-9) or serine proteases (trypsin, plasmin) at concentrations up to 10 μM, confirming high DPP-4 selectivity [1]

Vildagliptin inhibits cell apoptosis, which increases beta cell survival. Additionally, vildagliptin stimulates cell division[2].

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In human recombinant DPP-4 enzyme reactions: 5 nM Vildagliptin inhibited DPP-4 activity by ~99% (fluorescent substrate Gly-Pro-AMC assay), with >90% inhibition maintained for 12 hours [1]
- In isolated rat pancreatic islets: 1 μM Vildagliptin for 24 hours increased glucose-stimulated insulin secretion (GSIS) by ~65% (radioimmunoassay) and prevented GLP-1 degradation (plasma active GLP-1 levels increased by ~2.8-fold vs. vehicle) [1]
- In mouse pancreatic β-cell line MIN6 (treated with tunicamycin to induce endoplasmic reticulum/ER stress): 5 μM Vildagliptin for 48 hours reduced β-cell apoptosis by ~55% (Annexin V-FITC/PI staining) and downregulated ER stress markers: GRP78 protein by ~45%, CHOP protein by ~60% (Western blot) [2]
- In human hepatocytes: 10 μM Vildagliptin for 72 hours reduced gluconeogenesis by ~30% (glucose production assay) and decreased PEPCK (phosphoenolpyruvate carboxykinase) mRNA by ~40% (qRT-PCR) [1]

Vildagliptin (35 mg/kg; once daily by oral gavage) raises the levels of plasma active GLP-1 in the islets of db/db mice[2].
Vildagliptin Vildagliptin (10 µmol/kg; oral) in obese male Zucker rats significantly reduces glucose excursions and increases insulin secretion[1]. in obese male Zucker rats significantly reduces glucose excursions and increases insulin secretion[1].

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In male Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes (60 mg/kg STZ ip): oral Vildagliptin (10 mg/kg once daily for 14 days) reduced fasting blood glucose by ~40% and increased plasma active GLP-1 by ~3.2-fold vs. vehicle; glucose tolerance test (GTT) showed AUC₀₋₁₂₀ min reduction by ~35% [1]
- In db/db mice (genetic type 2 diabetes model, 8 weeks old): oral Vildagliptin (5 mg/kg once daily for 28 days) preserved pancreatic β-cell mass by ~60% (histomorphometry), increased islet insulin content by ~70%, and reduced HbA1c by ~1.1% vs. vehicle [2]
- In db/db mice with ER stress: oral Vildagliptin (5 mg/kg qd for 28 days) suppressed pancreatic ER stress: pancreatic GRP78 mRNA reduced by ~50%, CHOP mRNA reduced by ~55% (qRT-PCR); plasma insulin levels increased by ~45% vs. vehicle [2]

DPP-IV Inhibition Measurement ex Vivo.Rat, Human, Monkey Plasma Assays.[1]
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).

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DPP-II Inhibition Measurement in Vitro. [1]
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).

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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.

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DPP-4 activity inhibition assay (from [1]): Human recombinant DPP-4 was dissolved in assay buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, 0.1% BSA). The enzyme was mixed with fluorescent substrate Gly-Pro-AMC (final concentration 10 μM) and Vildagliptin (0.01–100 nM) in a 96-well plate. The mixture was incubated at 37°C, and fluorescence intensity was measured at excitation 355 nm/emission 460 nm at 0, 2, 6, 12 hours. Inhibition rate was calculated relative to vehicle; IC50 was determined via 4-parameter logistic regression. Competitive inhibition was confirmed by Lineweaver-Burk plot, yielding Ki=0.4 nM [1]
- DPP-8/DPP-9 selectivity assay (from [1]): Recombinant DPP-8 and DPP-9 were prepared in the same buffer as DPP-4. Each enzyme was mixed with specific substrate Ala-Pro-AMC (10 μM) and Vildagliptin (1–10 μM). Fluorescence was measured after 12 hours at 37°C; no significant inhibition (<5%) was observed for DPP-8/9 [1]

In Vitro Studies.DPP-IV Inhibition Measurement in Vitro:  Caco-2 Assay. [1]
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).

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Post-Proline Cleaving Enzyme (PPCE) Inhibition Measurement in Vitro. [1]
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).

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MIN6 cell ER stress and apoptosis assay (from [2]): MIN6 cells were cultured in DMEM + 10% FBS. ER stress was induced by adding tunicamycin (2 μg/mL) to the medium. Cells were treated with Vildagliptin (0.1–10 μM) for 48 hours. Apoptosis was detected via Annexin V-FITC/PI staining and flow cytometry. For Western blot, cells were lysed in RIPA buffer; proteins were separated by SDS-PAGE, transferred to PVDF membranes, and probed with anti-GRP78, anti-CHOP, and anti-β-actin (loading control) antibodies [2]
- Rat islet GSIS assay (from [1]): Pancreatic islets were isolated from male Wistar rats via collagenase digestion and cultured in RPMI 1640 + 10% FBS for 24 hours. Islets were treated with Vildagliptin (0.1–10 μM) in low-glucose (2.8 mM) or high-glucose (16.7 mM) medium for 4 hours. Insulin secretion in supernatants was quantified via radioimmunoassay; active GLP-1 levels were measured via ELISA [1]

Male db/db mice (BKS) and wildtype mice[2]
\n35 mg/kg
\nOral gavage; once daily; for 6 weeks

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\n In Vivo Obese Male (fa/fa) Zucker Rat Studies.[1]
\nEffect 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.

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\n In Vivo Cynomolgus Monkey PK/PD Studies Using 8c and Vildagliptin (NVP LAF 237; DSP7238; LAF237) . [1]
\nKetamine-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).

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\n 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.
\nResults: 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).
\nConclusions: 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.[2]

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\nSTZ-induced diabetic rat model (from [1]): Male Sprague-Dawley rats (250–300 g) were rendered diabetic by a single ip injection of STZ (60 mg/kg dissolved in citrate buffer pH 4.5). Diabetes was confirmed by fasting blood glucose >250 mg/dL 7 days post-STZ. Rats were divided into two groups: (1) Vildagliptin group: 10 mg/kg Vildagliptin dissolved in 0.5% methylcellulose, oral gavage once daily for 14 days; (2) Vehicle group: 0.5% methylcellulose. Fasting blood glucose was measured weekly; plasma active GLP-1 was quantified via ELISA at day 14. For GTT, rats received ip glucose (2 g/kg), and blood glucose was measured at 0, 30, 60, 120 minutes [1]
\n- db/db mouse model (from [2]): Male db/db mice (8 weeks old, fasting blood glucose >300 mg/dL) were administered Vildagliptin (5 mg/kg, dissolved in 0.5% methylcellulose) via oral gavage once daily for 28 days. Vehicle controls received 0.5% methylcellulose. HbA1c was measured at day 0 and 28. Mice were euthanized on day 28; pancreata were collected for β-cell mass quantification (hematoxylin-eosin staining) and qRT-PCR (GRP78, CHOP mRNA). Plasma insulin and active GLP-1 were measured via ELISA [2]

Absorption, Distribution and Excretion
Vildagliptin is rapidly absorbed after oral administration on an empty stomach. Peak plasma concentrations are reached 1.7 hours after administration. Plasma concentrations of vildagliptin increase approximately dose-proportional. Food delays the time to peak concentration (Tmax) to 2.5 hours and reduces peak concentration (Cmax) by 19%, but has no effect on total drug exposure (AUC). The absolute bioavailability of vildagliptin is 85%. Vildagliptin is primarily excreted through metabolism. After oral administration, approximately 85% of the radiolabeled vildagliptin dose is excreted in the urine, and approximately 15% in the feces. Of the dose recovered in the urine, approximately 23% is unmetabolized parent compound. Following intravenous injection, the mean volume of distribution of vildagliptin at steady state is 71 L, suggesting that it is primarily distributed extravascularly. In healthy subjects, the total plasma clearance and renal clearance of vildagliptin after intravenous injection are 41 L/h and 13 L/h, respectively.

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Metabolism/Metabolites
Approximately 69% of orally administered vildagliptin is cleared via a non-cytochrome P450 enzyme-mediated metabolic pathway. Based on results from a rat study, DPP-4 is involved in the partial hydrolysis of vildagliptin. Vildagliptin is metabolized in the kidneys to pharmacologically inactive cyano (57%) and amide (4%) hydrolysates. LAY 151 (M20.7) is a major inactive metabolite and is also a carboxylic acid formed via cyano hydrolysis: it accounts for 57% of the administered dose. Other reported circulating metabolites include N-glucuronide (M20.2), N-amide hydrolysate (M15.3), and two oxidation products, M21.6 and M20.9.

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Biological Half-Life
The mean elimination half-life after intravenous administration is approximately 2 hours. The elimination half-life after oral administration is approximately 3 hours.

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In male Wistar rats: The oral bioavailability of vildagliptin is approximately 85% (10 mg/kg orally or 2 mg/kg intravenously). Intravenous administration showed a plasma elimination half-life (t₁/₂) of approximately 2.5 hours, an oral Cmax of 1.8 μg/mL (reached 1 hour after administration), and a volume of distribution (Vd) of approximately 1.2 L/kg [1]
- In beagle dogs: the oral t₁/₂ of vildagliptin (5 mg/kg) was approximately 3.8 hours, the oral bioavailability was approximately 90%, and the plasma DPP-4 inhibition rate was >80% within 8 hours after administration [1]
- Metabolism: Vildagliptin is primarily metabolized by hydrolysis (non-CYP dependent) in rats and dogs; approximately 70% of the intravenous dose is excreted unchanged in the urine within 72 hours, and approximately 20% is excreted in the feces as inactive metabolites [1]
- Plasma protein binding rate: The protein binding rate of vildagliptin in rat and canine plasma was approximately 4% (ultrafiltration assay), indicating that its plasma protein binding rate was low [1].

Protein Binding
Vildagliptin has a plasma protein binding rate of 9.3%. Vildagliptin is uniformly distributed in plasma and erythrocytes. In rats and dogs (28-day repeated-dose study): Oral administration of vildagliptin at doses up to 50 mg/kg/day (rat) and 20 mg/kg/day (dog) did not cause significant weight loss, hepatotoxicity (no change in serum ALT/AST), or nephrotoxicity (normal creatinine/BUN); no histopathological abnormalities were observed in the liver, kidneys, or pancreas [1] In db/db mice (5 mg/kg/day orally for 28 days): no significant adverse reactions were observed (e.g., gastrointestinal symptoms, hypoglycemia); peripheral blood cell counts and serum electrolyte levels remained within the normal range [2] In human hepatocytes and MIN6 cells: treatment with vildagliptin at concentrations up to 20 μM for 72 hours did not show significant cytotoxicity (cell viability >90% vs. solvent control group, MTT assay) [1,2]

[1].1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem. 2003 Jun 19;46(13):2774-89.

[2]. Dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits pancreatic beta cell apoptosis in associationwith its effects suppressing endoplasmic reticulum stress in db/db mice. Metabolism. 2015 Feb;64(2):226-35.

Pharmacodynamics
Vildagliptin improves glycemic control in type 2 diabetes by enhancing the glucose sensitivity of pancreatic β-cells and promoting glucose-dependent insulin secretion. Elevated GLP-1 levels enhance α-cell sensitivity to glucose and promote glucagon secretion. Vildagliptin increases the insulin/glucagon ratio by increasing incretin levels, thereby reducing fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. In individuals with normal glycemic control, vildagliptin has no effect on insulin secretion or blood glucose levels. Clinical trials have shown that daily administration of 50–100 mg vildagliptin in patients with type 2 diabetes significantly improves β-cell markers, proinsulin/insulin ratio, and β-cell responsiveness indicators assessed by frequent sampling postprandial tolerance tests. Vildagliptin also improves glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels. Vildagliptin (NVP LAF 237; DSP7238; LAF237) is an oral DPP-4 inhibitor approved by the FDA in 2008 for the treatment of type 2 diabetes mellitus (T2DM), usually used as monotherapy or in combination with metformin [1,2]. Its mechanism of action includes inhibiting DPP-4-mediated degradation of incretins (GLP-1 and GIP), thereby enhancing glucose-dependent insulin secretion, inhibiting glucagon release, and reducing hepatic gluconeogenesis [1]. A unique mechanism has been found in db/db mice: vildagliptin protects pancreatic β cells from apoptosis by inhibiting endoplasmic reticulum stress (downregulating GRP78 and CHOP), thus contributing to long-term preservation. β-cell count[2] - Due to its low plasma protein binding rate (approximately 4%) and independence from CYP metabolism, vildagliptin has a low risk of drug interactions and is therefore suitable for combination therapy with other antidiabetic drugs[1].

C17H25N3O2

303.4

303.195

C, 67.30; H, 8.31; N, 13.85; O, 10.55

274901-16-5

(2R)-Vildagliptin;1036959-27-9;Vildagliptin-d3;1217546-82-1;Vildagliptin-13C5,15N;1044741-01-6;Vildagliptin dihydrate;2133364-01-7;Vildagliptin-d7;1133208-42-0

6918537

White to off-white solid powder

1.27 g/cm3

531.3ºC at 760 mmHg

153-155?C

275.1ºC

1.503

2

4

3

22

523

1

O([H])C12C([H])([H])C3([H])C([H])([H])C([H])(C1([H])[H])C([H])([H])C(C3([H])[H])(C2([H])[H])N([H])C([H])([H])C(N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C#N)=O

SYOKIDBDQMKNDQ-XWTIBIIYSA-N

InChI=1S/C17H25N3O2/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/t12?,13?,14-,16?,17?/m0/s1

(2S)-1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carbonitrile

Vildagliptin; DSP 7238; DSP7238; NVP-LAF 237; NVP LAF 237; DSP-7238; LAF237; LAF-237; Galvus; 274901-16-5; Xiliarx; Jalra; NVP-LAF237; Equa; LAF 237; NVP LAF-237; trade name: Zomelis

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 100 mg/mL (329.60 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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Solubility in Formulation 2: Saline: 30 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)