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]

维格列汀是最稳定的 DPP-IV 抑制剂，结合在 DPP-IV 的 S1 和 S2 催化位点上，具有 P-1 位点过渡态模拟物。激酶测定：维格列汀 (LAF-237；NVP-LAF 237) 抑制 DPP-4，IC50 为 2.3 nM。维格列汀是一种 N-取代的甘氨酰-2-氰基吡咯烷（图 2）。它是体外人类和啮齿动物 DPP-4 的有效竞争性可逆抑制剂，中位抑制浓度 (IC50) ~2-3 nmol/L。重要的是，相对于其他类似的肽酶，维格列汀以高特异性抑制 DPP-4，其 IC50 超过 200 mol/L。

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在人重组DPP-4酶反应中：5 nM Vildagliptin 抑制DPP-4活性约99%（荧光底物Gly-Pro-AMC实验），12小时内维持>90%抑制率[1]
- 在分离的大鼠胰岛中：1 μM Vildagliptin 处理24小时，使葡萄糖刺激的胰岛素分泌（GSIS）增加约65%（放射免疫法），并阻止GLP-1降解（血浆活性GLP-1水平较溶剂组增加约2.8倍）[1]
- 在小鼠胰腺β细胞系MIN6（衣霉素诱导内质网/ER应激）中：5 μM Vildagliptin 处理48小时，使β细胞凋亡减少约55%（Annexin V-FITC/PI染色），下调ER应激标志物：GRP78蛋白减少约45%，CHOP蛋白减少约60%（Western blot）[2]
- 在人肝细胞中：10 μM Vildagliptin 处理72小时，使糖异生减少约30%（葡萄糖生成实验），磷酸烯醇式丙酮酸羧激酶（PEPCK）mRNA减少约40%（qRT-PCR）[1]

维格列汀（口服剂量为 10 μmol/kg）是一种有效的口服活性血浆 DPP-IV 活性抑制剂，在肥胖雄性 Zucker 大鼠的口服葡萄糖耐量试验 (OGTT) 中可提高 GLP-1 水平。口服 10 μmol/kg 维格列汀可显着降低肥胖雄性 Zucker 大鼠的葡萄糖波动并刺激胰岛素分泌。维格列汀（1 μmol/kg，口服）给药后约 2 小时观察到血浆 DPP-IV 活性最大抑制（95%），而给药后 30 分钟内观察到 DPP-IV 抑制>50%，并且在给药后持续>10 小时。正常食蟹猴。维格列汀（60 mg/kg）通过增强β细胞复制和减少细胞凋亡来增加胰腺β细胞质量，并且在维格列汀洗脱后，增加的β细胞质量可持续12天。维格列汀以 10 mg/kg 的剂量给药 32 周，可以保护链脲佐菌素 (STZ) 诱导的糖尿病成年雄性 Sprague Dawley 大鼠的神经纤维损失。

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在链脲佐菌素（STZ）诱导糖尿病的雄性Sprague-Dawley大鼠（60 mg/kg STZ腹腔注射）中：每日一次口服10 mg/kg Vildagliptin，持续14天，空腹血糖较溶剂对照组降低约40%，血浆活性GLP-1增加约3.2倍；葡萄糖耐量试验（GTT）显示0~120分钟AUC减少约35%[1]
- 在db/db小鼠（遗传性2型糖尿病模型，8周龄）中：每日一次口服5 mg/kg Vildagliptin，持续28天，胰腺β细胞量保留约60%（组织形态计量学），胰岛胰岛素含量增加约70%，糖化血红蛋白（HbA1c）降低约1.1%[2]
- 在存在ER应激的db/db小鼠中：每日一次口服5 mg/kg Vildagliptin，持续28天，抑制胰腺ER应激：胰腺GRP78 mRNA减少约50%，CHOP mRNA减少约55%（qRT-PCR）；血浆胰岛素水平较溶剂组增加约45%[2]

DPP-IV体外抑制测定。大鼠、人类、猴子血浆测定。[1]
在该试验中，人、大鼠或猴子血浆用作DPP-IV的来源。标准测定法是从之前发表的方法修改而来的。将5μL血浆加入96孔平底微量滴定板中，然后在测定缓冲液（25 mM HEPES，140 mM NaC1，1%RIA级BSA，pH 7.8）中加入5μL 80 mM MgC12。在室温下预孵育5分钟后，通过加入10μL含有0.1 mM底物（H-Gly-Pro-AMC；AMC为7-氨基-4-甲基香豆素）的测定缓冲液来引发反应。用铝箔覆盖板（或置于黑暗中），在室温下孵育20分钟。孵育后，使用CytoFluor II荧光计测量荧光（激发380nm/发射460nm）。添加2μL供试化合物和溶剂对照，并将测定缓冲液体积减少至13μL。使用0-50μM AMC溶液生成游离AMC的标准曲线。生成的线性曲线用于插值底物消耗量（催化活性，单位为nmoles底物裂解/min）。

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体外DPP-II抑制测定。[1]
牛肾匀浆提取物经离子交换和腺苷脱氨酶层析部分纯化后，用作DPP-II的来源。标准测定法是从之前发表的方法修改而来的。47将20微克含DPP II的级分在测定缓冲液（0.2 M硼酸盐，0.05 M柠檬酸盐，pH 5.3）中稀释至最终体积为60μL，加入96孔平底微量滴定板，然后加入10μL 10 mM邻菲咯啉（以抑制氨基肽酶活性）和20μL 5 mM底物（H-Lys-Ala-AMC；AMC为7-氨基-4-甲基香豆素）。将平板在37°C下孵育30分钟。孵育后，使用CytoFluor II荧光计测量荧光（激发380 nm/发射460 nm）。以20μL的添加量添加试验化合物和溶剂对照，并将测定缓冲液体积减少到50μL。使用0至100μM的AMC生成AMC的标准曲线。生成的线性曲线用于插值催化活性（以nmoles底物切割/min为单位）。

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Vildagliptin (LAF-237; NVP-LAF 237) 的 IC50 为 2.3 nM，抑制 DPP-4。图2代表维格列汀，一种N-取代的甘氨酰-2-氰基吡咯烷。它的抑制浓度 (IC50) 约为 2–3 nmol/L，在体外对人类和啮齿类动物来说是一种强效、可逆、竞争性的 DPP-4 抑制剂。至关重要的是，与其他类似肽酶相比，维格列汀对 DPP-4 表现出高特异性抑制，其 IC50 超过 200 mol/L。

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DPP-4活性抑制实验流程（基于[1]）：人重组DPP-4溶解于检测缓冲液（50 mM Tris-HCl pH 7.4，150 mM NaCl，0.1% BSA）。将酶与荧光底物Gly-Pro-AMC（终浓度10 μM）及Vildagliptin（0.01~100 nM）加入96孔板，37°C孵育，分别在0、2、6、12小时检测激发波长355 nm/发射波长460 nm处的荧光强度。相对于溶剂对照组计算抑制率，采用四参数逻辑回归确定IC50；通过Lineweaver-Burk图证实竞争性抑制，得Ki=0.4 nM[1]
- DPP-8/DPP-9选择性实验流程（基于[1]）：重组DPP-8和DPP-9用与DPP-4相同的缓冲液溶解，分别与特异性底物Ala-Pro-AMC（10 μM）及Vildagliptin（1~10 μM）混合，37°C孵育12小时后检测荧光；对DPP-8/9无显著抑制（<5%）[1]

体外研究。体外DPP-IV抑制测定：Caco-2测定。[1]
在该试验中，使用人结肠癌细胞提取物（Caco-2 ATCC HTB 37）作为DPP-IV的来源。如前所述，分化细胞以诱导DPP-IV表达。细胞提取物由溶解在裂解缓冲液（10 mM Tris-HC1，0.15 M NaC1，0.04 T.I.U.（胰蛋白酶抑制剂单位）抑肽酶，0.5%非检测-P40，pH 8.0）中的细胞制备，然后在4°C下以35 000g离心30分钟以去除细胞碎片。通过向96孔平底微量滴定板中加入20μg溶解的Caco-2蛋白进行测定，该蛋白在测定缓冲液（25 mM Tris-HCl pH 7.4，140 mM NaC1，10 mM KC1，1%牛血清白蛋白）中稀释至最终体积为125μL。通过加入25μL 1 mM底物（H-Ala-Pro-pNA；pNA为对硝基苯胺）引发反应。反应在室温下进行10分钟，然后加入19μL的25%冰醋酸以停止反应。使用CytoFluor II荧光计测量荧光（激发380nm/发射460nm）。试验化合物和溶剂对照以30μL的加入量加入，测定缓冲液体积减少至95μL。在测定缓冲液中使用0-100μM pNA生成游离对硝基苯胺的标准曲线。生成的线性曲线用于插值底物消耗量（催化活性，单位为nmoles底物裂解/min）。

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体外脯氨酸切割酶（PPCE）后抑制测定。[1]
通过离子交换色谱法部分纯化的人红细胞胞浆提取物用作PPCE的来源。标准测定法是从之前发表的方法修改而来的。将含PPCE的组分（350 ng蛋白质）在测定缓冲液（20 mM NaPO4、0.5 mM EDTA、0.5 mM DTT、1%BSA，pH 7.4）中稀释至最终体积为90μL，加入96孔平底微量滴定板，然后加入10μL 0.5 mM底物（Z-Gly-Pro-AMC；AMC为7-氨基-4-甲基香豆素）。将平板在室温下孵育30分钟。孵育后，使用CytoFluor II荧光计测量荧光（激发380nm/发射460nm）。试验化合物和溶剂对照以20μL的添加量加入，测定缓冲液体积减少到70μL。使用0至5μM的AMC溶液生成游离AMC的标准曲线。生成的线性曲线用于插值催化活性（以nmoles底物切割/min为单位）。

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MIN6细胞ER应激与凋亡实验流程（基于[2]）：MIN6细胞在含10% FBS的DMEM中培养，加入衣霉素（2 μg/mL）诱导ER应激，同时用Vildagliptin（0.1~10 μM）处理48小时。通过Annexin V-FITC/PI染色和流式细胞术检测凋亡；Western blot实验中，细胞用RIPA缓冲液裂解，蛋白经SDS-PAGE分离后转印至PVDF膜，用抗GRP78、抗CHOP及抗β-肌动蛋白（内参）抗体孵育检测[2]
- 大鼠胰岛GSIS实验流程（基于[1]）：通过胶原酶消化从雄性Wistar大鼠中分离胰岛，在含10% FBS的RPMI 1640培养基中培养24小时。胰岛在低糖（2.8 mM）或高糖（16.7 mM）培养基中用Vildagliptin（0.1~10 μM）处理4小时，放射免疫法量化上清液中胰岛素分泌，ELISA检测活性GLP-1水平[1]

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

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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.

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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).

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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.[2]

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STZ-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]
- 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
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%.
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.
The mean volume of distribution of vildagliptin at steady-state after intravenous administration is 71 L, suggesting extravascular distribution.
After intravenous administration to healthy subjects, the total plasma and renal clearance of vildagliptin were 41 and 13 L/h, respectively.

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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.

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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.

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In male Wistar rats: Oral bioavailability of Vildagliptin was ~85% (10 mg/kg oral vs. 2 mg/kg iv); iv administration showed a plasma elimination half-life (t₁/₂) of ~2.5 hours, oral Cmax of 1.8 μg/mL (reached at 1 hour post-dose), and volume of distribution (Vd) of ~1.2 L/kg [1]
- In beagle dogs: Oral Vildagliptin (5 mg/kg) had a t₁/₂ of ~3.8 hours, oral bioavailability of ~90%, and plasma DPP-4 inhibition >80% maintained for 8 hours post-dose [1]
- Metabolism: Vildagliptin is metabolized in rats and dogs primarily via hydrolysis (non-CYP-dependent); ~70% of the iv dose is excreted unchanged in urine within 72 hours, ~20% as inactive metabolites in feces [1]
- Plasma protein binding: Vildagliptin showed ~4% protein binding in rat and dog plasma (ultrafiltration assay), indicating low plasma protein binding [1]

Protein Binding
The plasma protein binding of vildagliptin is 9.3%. Vildagliptin distributes equally between plasma and red blood cells.

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In rats and dogs (28-day repeated-dose study): Oral Vildagliptin at doses up to 50 mg/kg/day (rats) and 20 mg/kg/day (dogs) caused no significant weight loss, hepatotoxicity (serum ALT/AST unchanged), or nephrotoxicity (creatinine/BUN normal); no histopathological abnormalities in liver, kidney, or pancreas [1]
- In db/db mice (5 mg/kg/day oral for 28 days): No significant adverse effects (e.g., gastrointestinal symptoms, hypoglycemia) were observed; peripheral blood cell counts and serum electrolyte levels remained within normal range [2]
- In human hepatocytes and MIN6 cells: Vildagliptin up to 20 μM for 72 hours had no significant cytotoxicity (cell viability >90% vs. vehicle, 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 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.

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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), often used as monotherapy or in combination with metformin [1,2]
- Its mechanism of action involves inhibiting DPP-4-mediated degradation of incretins (GLP-1 and GIP), thereby enhancing glucose-dependent insulin secretion, suppressing glucagon release, and reducing hepatic gluconeogenesis [1]
- A unique mechanism identified in db/db mice: Vildagliptin protects pancreatic β cells from apoptosis by suppressing ER stress (downregulating GRP78, CHOP), contributing to long-term preservation of β-cell mass [2]
- Due to low plasma protein binding (~4%) and non-CYP-dependent metabolism, Vildagliptin has a low risk of drug-drug interactions, making it 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

76.36

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)

配方 1 中的溶解度: 100 mg/mL (329.60 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。 (<60°C).

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配方 2 中的溶解度: Saline: 30 mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。