Sitagliptin

Catalog No.S5079 Batch:S507904

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Technical Data

Formula

C16H15F6N5O
Molecular Weight 407.31 CAS No. 486460-32-6
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
DPP-4 [1]
(Cell-free)
18 nM
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].

Protocol (from reference)

Cell Assay:

[5]
  • Cell lines

    CD4+ T-cells

  • Concentrations

    100 μmol/l

  • Incubation Time

    1 h

  • Method

    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.
Animal Study:

[4]
  • Animal Models

    male ICR mice

  • Dosages

    280 mg/kg

  • Administration

    oral

Selleck's Sitagliptin has been cited by 18 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.