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受注：045-509-1970 |
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化学情報
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Synonyms | MK-0431 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C16H15F6N5O |
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| 分子量 | 407.31 | CAS No. | 486460-32-6 | |
| Solubility (25°C)* | 体外 | DMSO | 81 mg/mL (198.86 mM) | |
| Ethanol | 81 mg/mL (198.86 mM) | |||
| Water | 7 mg/mL (17.18 mM) | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Sitagliptin (MK-0431) is an oral and highly selective DPP-4 inhibitor with an IC50 of 18 nM. It is used for the treatment of type 2 diabetes. |
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| in vitro | Sitagliptin exhibits a > 2600-fold margin of selectivity against DPP8, DPP9, and other members of the dipeptidyl peptidase family (i.e., potency against DPP-4 vs. DPP8/9)[1]. MK0431 reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involving cAMP/PKA/Rac1 activation[2]. Sitagliptin exerts a novel, direct action in order to stimulate GLP-1 secretion by the intestinal L cell through a DPP-4-independent, protein kinase A- and MEK-ERK1/2-dependent pathway. It therefore reduces the effect of autoimmunity on graft survival[3]. |
| in vivo | Sitagliptin is well absorbed after oral administration with a bioavailability of 87%. Sitagliptin has an apparent terminal half-life of 10–12 h at doses of 25-100 mg and is excreted mainly (≈ 80%) as unchanged compound by the kidneys. Sitagliptin does not interfere with the P450 cytochrome enzymes nor have there been any reported significant drug-drug interactions. Sitagliptin has been shown to inhibit DPP-4 activity by > 90% within 1-2 h of administration[1]. It has a short half-life in mice (1-2 h). Chronic sitagliptin treatment in a non-geneticmouse model of type 2 diabetes elicits significant improvement in glycemic control. The improved glucose homeostasis correlates with restoration of normal islet cell (α and β cells) mass, architecture and insulin secretion capacity in response to glucose stimulation[4]. Sitagliptin prolongs islet graft survival in streptozotocin-induced and NOD mice. Administration of sitagliptin in vivo reduces lymph node and splenic CD4+ T-cell migration, measured in vitro, via incretin- and nonincretin-mediated effects, respectively, and splenic sDPP-IV-responsive CD4+ T-cells and lymph node incretin nonresponsive CD4+ T-cells selectively infiltrated islets of diabetic NOD mice, after tail vein injection[5]. Sitagliptin significantly suppressed epileptogenesis in PTZ (pentylenetetrazole)-induced seizures. Sitagliptin counteracted neuronal damage and all biochemical, and histo-chemical alteration induced by PTZ. Oral sitagliptin can promote hippocampal neurogenesis, counteract hippocampal oxidative stress, and prevent the decline in mice cognition[6]. |
プロトコル(参考用のみ)
| 細胞アッセイ | 細胞株 | CD4+ T-cells |
|---|---|---|
| 濃度 | 100 μmol/l | |
| 反応時間 | 1 h | |
| 実験の流れ | CD4+ T-cells (1 × 106 cells) were plated on membrane inserts (8-μm pore size) in serum-free RPMI 1640 medium. Cell migration was assayed using Transwell chambers in media ± purified porcine kidney DPP-IV (32.1 units/mg; 100 mU/ml final concentration) ± sitagliptin (100 μmol/l) or human GIP (100 nmol/l) or human GLP-1 (100 nmol/l). After 1 h, cells on the upper surface were removed mechanically and migrated cells in the lower compartment were counted. |
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| 動物実験 | 動物モデル | male ICR mice |
| 投薬量 | 280 mg/kg | |
| 投与方法 | oral |
参考
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Untersuchungen zur Ursache der durch Dipeptidylpeptidase-4-Inhibitoren hervorgerufenen endothelialen Barrierestörung der Retina [ OPARU, 2024, 10.18725/OPARU-52005] | PubMed: none |
| miR-23b-3p Ameliorates LPS-Induced Pulmonary Fibrosis by Inhibiting EndMT via DPP4 Inhibition [ Mol Biotechnol, 2023, 10.1007/s12033-023-00992-9] | PubMed: 38150089 |
| Multi-target mode of action of Sulfodyne®, a stabilized Sulforaphane, against pathogenic effects of SARS-CoV-2 infection [ bioRxiv, 2023, 10.1101/2023.12.18.572126] | PubMed: none |
| Inhibition of CXXC5 function reverses obesity-related metabolic diseases [ Clin Transl Med, 2022, 12(4):e742] | PubMed: 35384342 |
| Nutritional control of thyroid morphogenesis through gastrointestinal hormones [ Curr Biol, 2022, S0960-9822(22)00137-3] | PubMed: 35196509 |
| A novel human stem cell-based biomarker assay for in vitro assessment of developmental toxicity [ Birth Defects Res, 2022, 10.1002/bdr2.2001] | PubMed: 35289129 |
| DPP4 Regulates DHCR24-Mediated Cholesterol Biosynthesis to Promote Methotrexate Resistance in Gestational Trophoblastic Neoplastic Cells [ Front Oncol, 2021, 11:704024] | PubMed: 34926239 |
| Functional Dissection of CD26 and Its Pharmacological Inhibition by Sitagliptin During Skin Wound Healing [ Med Sci Monit, 2021, 27:e928933] | PubMed: 33735157 |
| Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4. [ J Biol Chem, 2020, 10.1074/jbc.RA119.010894] | PubMed: 31988243 |
| Sitagliptin and the Blood-Retina Barrier: Effects on Retinal Endothelial Cells Manifested Only After Prolonged Exposure [ J Diabetes Res, 2020, 2020:2450781] | PubMed: 32566677 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。