受注:045-509-1970 |
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Synonyms | MK-0431 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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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 | 3 mg/mL (7.36 mM) | |||
* <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. |
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]. |
細胞アッセイ | 細胞株 | CD4+ T-cells |
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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 |
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。
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