ArticleEndocrinology, diabetes & metabolism2018
A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice.
Article in Endocrinology, diabetes & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 88 citations in OpenAlex.
- In Silico Identification of Novel Leads as Potential DPP-IV Inhibitors as Antidiabetic Agents Using Virtual Screening.ACS omega · 2026Article
- Preclinical Modeling and Simulation to Explore the Tissue/Plasma Exposure and Pharmacodynamic Effect of Vildagliptin in Diabetes Treatment.CPT: pharmacometrics & systems pharmacology · 2026Article
- The Role of Immunosenescence and Inflammaging in the Susceptibility of Older Adults to SARS-CoV-2 Infection.Current pharmaceutical biotechnology · 2026Review
- Triazole Scaffold-based DPP-IV Inhibitors for the Management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR.Current topics in medicinal chemistry · 2026Review
- Zebrafish as a translational model for peptide-mediated synaptic dysfunction related to obesity.Frontiers in synaptic neuroscience · 2026Review
- Bioprospection of indigenous herbal formulations for diabetes care: in vitro, network pharmacology, and molecular dynamics studies.BMC complementary medicine and therapies · 2025Article
- In-silico evaluation of diffractaic acid as novel anti-diabetic inhibitor against dipeptidyl peptidase IV enzyme.In silico pharmacology · 2025Article
- Cosolvent Molecular Dynamics Applied to DPP4, DPP8 and DPP9: Reproduction of Important Binding Features and Use in Inhibitor Design.Journal of chemical information and modeling · 2024Article
- Computational Modeling of the Interactions between DPP IV and Hemorphins.International journal of molecular sciences · 2024Article
- Machine learning assessment of vildagliptin and linagliptin effectiveness in type 2 diabetes: Predictors of glycemic control.PloS one · 2024Article
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- Nitriles: an attractive approach to the development of covalent inhibitors.RSC medicinal chemistry · 2023Review
- Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches.Molecules (Basel, Switzerland) · 2023Article
- DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature.Frontiers in molecular biosciences · 2023Review
- Novel hit of DPP-4Is as promising antihyperglycemic agents with dual antioxidant/anti-inflammatory effects for type 2 diabetes with/without COVID-19.Bioorganic chemistry · 2022Article
- The Potential Role of Cyclopeptides fromMetabolites · 2022Article
- Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4).Pharmaceuticals (Basel, Switzerland) · 2022Article
- Docking-generated multiple ligand poses for bootstrapping bioactivity classifying Machine Learning: Repurposing covalent inhibitors for COVID-19-related TMPRSS2 as case study.Computational and structural biotechnology journal · 2021Article
- Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSince 2006, DPP-4 inhibitors have become established therapy for the treatment of type 2 diabetes. Despite sharing a common mechanism of action, considerable chemical diversity exists amongst members of the DPP-4 inhibitor class, raising the question as to whether structural differences may result in differentiated enzyme inhibition and antihyperglycaemic activity.
methodsWe have compared the binding properties of the most commonly used inhibitors and have investigated the relationship between their inhibitory potency at the level of the enzyme and their acute glucose-lowering efficacy.
resultsFirstly, using a combination of published crystal structures and in-house data, we demonstrated that the binding site utilized by all of the DPP-4 inhibitors assessed was the same as that used by neuropeptide Y, supporting the hypothesis that DPP-4 inhibitors are able to competitively inhibit endogenous substrates for the enzyme. Secondly, we ascertained that the enzymatic cleft of DPP-4 is a relatively large cavity which displays conformational flexibility to accommodate structurally diverse inhibitor molecules. Finally, we found that for all inhibitors, irrespective of their chemical structure, the inhibition of plasma DPP-4 enzyme activity correlates directly with acute plasma glucose lowering in mice.
conclusionThe common binding site utilized by different DPP-4 inhibitors enables similar competitive inhibition of the cleavage of the endogenous DPP-4 substrates. Furthermore, despite chemical diversity and a range of binding potencies observed amongst the DPP-4 inhibitors, a direct relationship between enzyme inhibition in the plasma and glucose lowering is evident in mice for each member of the classes studied.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.