Sitagliptin (MK0431)
(Synonyms: 西格列汀; MK-0431) 目录号 : GC31317
Sitagliptin (MK0431) 是一种口服、高选择性的二肽基肽酶-4（DPP-4）抑制剂，IC50为18nM。
Cas No.:486460-32-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Sitagliptin (MK0431) is an oral and highly selective Dipeptidyl peptidase-4 (DPP-4) inhibitor with an IC50 of 18nM[1]. DPP-4 is a serine protease that rapidly degrades the incretin hormones GLP-1 and GIP, making it a key therapeutic target for type 2 diabetes[2]. Sitagliptin is mainly used in type 2 diabetes research[3].
In vitro, Sitagliptin (100μM; 1h) abolished porcine DPP-IV–stimulated CD4⁺ T-cell migration and intracellular cAMP accumulation without altering basal PKA activity or GLP-1/GIP-mediated signaling[4]. In isolated human islets cultured for 10 weeks, Sitagliptin (1µM) increased functional β-cell number, raised insulin content, elevated PDX-1+/insulin+ and Nkx6.1+/insulin+ cells, increased Ki67+ β-cells, and lowered TUNEL+ apoptotic β-cells without changing α-cell mass[5].
In vivo, Sitagliptin (100mg/kg; i.p.; 1h before SAP induction) alleviated oxidative stress and excessive autophagy in lung tissue of WT mice with SAP-ALI, activated the p62–Keap1–Nrf2 pathway, and promoted Nrf2 nuclear translocation[6]. Sitagliptin (90mg/kg/day; orally; 180 days) reversed obesity-induced increases in visceral fat ratio, adipocyte size, macrophage infiltration, and serum IL-6, IL-1β, and TNF-α levels in high-fat-diet-fed immature mice[7].
References:
[1] Thomas L, Eckhardt M, Langkopf E, Tadayyon M, Himmelsbach F, Mark M. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther. 2008;325(1):175-182.
[2] Ahrén B. DPP-4 inhibitors. Best Pract Res Clin Endocrinol Metab. 2007;21(4):517-533.
[3] Scott LJ. Sitagliptin: A Review in Type 2 Diabetes. Drugs. 2017;77(2):209-224.
[4] Kim SJ, Nian C, Doudet DJ, McIntosh CH. Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes. 2009;58(3):641-651.
[5] Liu W, Lau HK, Son DO, et al. Combined use of GABA and sitagliptin promotes human β-cell proliferation and reduces apoptosis. J Endocrinol. 2021;248(2):133-143.
[6] Kong L, Deng J, Zhou X, et al. Sitagliptin activates the p62-Keap1-Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury. Cell Death Dis. 2021;12(10):928.
[7] Wang X, Weng W, Cui Y, Zou C. Sitagliptin Alleviates Obesity in Immature Mice by Inhibiting Oxidative Stress and Inflammation. Reprod Sci. 2024;31(11):3549-3559.
Sitagliptin (MK0431) 是一种口服、高选择性的二肽基肽酶-4（DPP-4）抑制剂，IC50为18nM[1]。DPP-4是一种丝氨酸蛋白酶，可快速降解肠促胰岛素GLP-1和GIP，因此成为2型糖尿病治疗的关键靶点[2]。Sitagliptin主要用于2型糖尿病的研究[3]。
在体外，Sitagliptin（100μM；1小时）可消除猪DPP-IV诱导的CD4⁺ T细胞迁移和细胞内cAMP积聚，而不影响基础PKA活性或GLP-1/GIP介导的信号传导[4]。在培养10周的分离人胰岛中，Sitagliptin（1μM）可增加功能性β细胞数量，提高胰岛素含量，增加PDX-1⁺/insulin⁺和Nkx6.1⁺/insulin⁺细胞比例，增加Ki67⁺ β细胞数量，并降低TUNEL⁺凋亡β细胞数量，但不改变α细胞质量[5]。
在体内，Sitagliptin（100mg/kg；腹腔注射；SAP诱导前1小时）可减轻WT小鼠SAP相关急性肺损伤（SAP-ALI）肺组织中的氧化应激和过度自噬，激活p62–Keap1–Nrf2通路，并促进Nrf2核转位[6]。Sitagliptin（90mg/kg/day；口服；180天）可逆转高脂饮食诱导的幼龄肥胖小鼠中内脏脂肪比例、脂肪细胞大小、巨噬细胞浸润以及血清IL-6、IL-1β和TNF-α水平的升高[7]。
| Cell experiment [1]: | |
Cell lines | CD4⁺ T-cells |
Preparation Method | For isolation of T-cells, spleen cell suspensions were prepared from female NOD mice. CD4⁺ T-cells were enriched using the Mouse CD4⁺ T Cell separation kit, and the purity of CD4⁺ T-cells was confirmed by flow cytometry. CD4⁺ T-cells were plated on membrane inserts (8μm poresize) in serum-free RPMI 1640, and cell migration was assayed using Transwell chambers in the presence or absence of purified porcine kidney DPP-IV (32.1units/mg; 100mU/ml final concentration)± DPP-IV inhibitor Sitagliptin (100μM). After 1h, cells on the upper surface were removed mechanically, and cells that had migrated into the lower compartment were counted. The extent of migration was then expressed relative to the control sample. cAMP concentration in the cell extracts was determined using the Parameter cyclic AMP assay kit. Protein kinase A(PKA) Activity was measured using a protein kinase A kinase activity assay kit. |
Reaction Conditions | 100μM; 1h |
Applications | Sitagliptin abolished porcine DPP-IV–stimulated CD4⁺ T-cell migration and intracellular cAMP accumulation without altering basal PKA activity. |
| Animal experiment [2]: | |
Animal models | Immature CD-1 mice |
Preparation Method | Immature CD-1 mice born from pregnant mice reared with HFD were used as modeling mice. Following being fed with HFD for 1 more week, the model of obese immature mice was considered successful if their body weight exceeded 20% of the average body weight of the control group. Three groups were divided: Control (offspring of pregnant mice were fed with normal diet), Obesity (obese immature mice were orally administered with the equal volume of normal saline every day for 180 days), and Obesity+90mg/kg Sitagliptin (obese immature mice were orally administered with 90mg/kg Sitagliptin per day for 180 days). Body weights of animals were recorded at the end the animal experiment. The number of animals in each group was 8. After serum of each animal was collected, serum biochemical indexes were detected using a biochemistry analyzer. A DEXA scanner was utilized to detect the visceral fat ratio of each mouse. The secretion of IL-6, TNF-α, MDA, and ADPN , as well as the activity of SOD were measured using the ELISA assay. Adipose tissues were collected for RT PCR, Western Blot and H&E Staining analyses. |
Dosage form | 90mg/kg/day; orally; 180 days |
Applications | Sitagliptin reversed obesity-induced increases in visceral fat ratio, adipocyte size, macrophage infiltration, and serum IL-6, IL-1β, and TNF-α levels in high-fat-diet-fed immature mice. |
References: | |
| Cas No. | 486460-32-6 | SDF | |
| 别名 | 西格列汀; MK-0431 | ||
| Canonical SMILES | O=C(N1CC2=NN=C(C(F)(F)F)N2CC1)C[C@H](N)CC3=CC(F)=C(F)C=C3F | ||
| 分子式 | C16H15F6N5O | 分子量 | 407.31 |
| 溶解度 | DMSO : ≥ 50 mg/mL (122.76 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4551 mL | 12.2757 mL | 24.5513 mL |
| 5 mM | 491 μL | 2.4551 mL | 4.9103 mL |
| 10 mM | 245.5 μL | 1.2276 mL | 2.4551 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet