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Sitagliptin

Name: Sitagliptin
Brand: Selleck Chemicals
SKU: S5079
Rating: 5 (14 reviews)

Catalog No.S5079 Synonyms: MK-0431

For research use only.

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.

CAS No. 486460-32-6

Selleck's Sitagliptin has been cited by 14 publications

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DPP Signaling Pathway Map

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 Research:

^[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 Research:

^[4]

Animal Models: male ICR mice
Dosages: 280 mg/kg
Administration: oral

References

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Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	407.31
Formula	C₁₆H₁₅F₆N₅O
CAS No.	486460-32-6
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)CC(CC3=CC(=C(C=C3F)F)F)N

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05219409	Not yet recruiting	Drug: Sitagliptin\|Device: Professional CGM	Type 1 Diabetes	University of Milan	December 2022	Phase 2\|Phase 3
NCT05403281	Completed	Drug: DW6012	Healthy Subjects	Dong Wha Pharmaceutical Co. Ltd.	November 5 2021	Phase 1
NCT03359590	Completed	Drug: Sitagliptin 100 mg\|Drug: Placebo	Pharmacological Action	Profil Institut für Stoffwechselforschung GmbH\|Merck Sharp & Dohme LLC	March 21 2018	Phase 2
NCT03659461	Completed	Drug: Sitagliptin	Type 2 Diabetes Mellitus\|PreDiabetes	National University of Malaysia	October 1 2017	Not Applicable
NCT03233178	Completed	Other: Non-interventional	T2DM (Type 2 Diabetes Mellitus)\|Fatty Liver\|NAFLD	LMC Diabetes & Endocrinology Ltd.	January 2017	--

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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