Autor segons l'article: Ojeda-Montes M, Gimeno A, Tomas-Hernández S, Cereto-Massagué A, Beltrán-Debón R, Valls C, Mulero M, Pujadas G, Garcia-Vallvé S
Departament: Bioquímica i Biotecnologia
Autor/s de la URV: Beltrán Debón, Raúl Alejandro / Cereto Massagué, Adrián José / Garcia Vallve, Santiago / Mulero Abellán, Miguel / OJEDA MONTES, Mª JOSÉ / Pujadas Anguiano, Gerard / TOMAS HERNÁNDEZ, SARA / Valls Bautista, Cristina
Paraules clau: User-computer interface Structure-activity relationship Incretins Hyperglycemia treatment Humans Glp-1 Gliptins Gip Drug evaluation, preclinical Dipeptidyl-peptidase iv inhibitors Dipeptidyl peptidase 4 Binding sites Animals Amino acid sequence hyperglycemia treatment glp-1 gliptins gip
Resum: The inhibition of dipeptidyl peptidase‐IV (DPP‐IV) has emerged over the last decade as one of the most effective treatments for type 2 diabetes mellitus, and consequently (a) 11 DPP‐IV inhibitors have been on the market since 2006 (three in 2015), and (b) 74 noncovalent complexes involving human DPP‐IV and drug‐like inhibitors are available at the Protein Data Bank (PDB). The present review aims to (a) explain the most important activity cliffs for DPP‐IV noncovalent inhibition according to the binding site structure of DPP‐IV, (b) explain the most important selectivity cliffs for DPP‐IV noncovalent inhibition in comparison with other related enzymes (i.e., DPP8 and DPP9), and (c) use the information deriving from this activity/selectivity cliff analysis to suggest how virtual screening protocols might be improved to favor the early identification of potent and selective DPP‐IV inhibitors in molecular databases (because they have not succeeded in identifying selective DPP‐IV inhibitors with IC50 ≤ 100 nM). All these goals are achieved with the help of available homology models for DPP8 and DPP9 and an analysis of the structure-activity studies used to develop the noncovalent inhibitors that form part of some of the complexes with human DPP‐IV available at the PDB.
Àrees temàtiques: Pharmacology & pharmacy Pharmacology Molecular medicine Medicina i General medicine Drug discovery Ciências biológicas ii Ciências biológicas i Chemistry, medicinal
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 01986325
Adreça de correu electrònic de l'autor: adrianjose.cereto@urv.cat cristina.valls@urv.cat miquel.mulero@urv.cat santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat raul.beltran@urv.cat
Identificador de l'autor: 0000-0001-5583-5695 0000-0002-0348-7497 0000-0003-2598-8089 0000-0001-9691-1906
Data d'alta del registre: 2024-09-07
Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
Enllaç font original: https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21499
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Referència a l'article segons font original: Medicinal Research Reviews. 38 (6): 1874-1915
Referència de l'ítem segons les normes APA: Ojeda-Montes M, Gimeno A, Tomas-Hernández S, Cereto-Massagué A, Beltrán-Debón R, Valls C, Mulero M, Pujadas G, Garcia-Vallvé S (2018). Activity and selectivity cliffs for DPP-IV inhibitors: Lessons we can learn from SAR studies and their application to virtual screening. Medicinal Research Reviews, 38(6), 1874-1915. DOI: 10.1002/med.21499
DOI de l'article: 10.1002/med.21499
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2018
Tipus de publicació: Journal Publications