Comparative in silico prediction of P-glycoprotein-mediated transport for 2010-2020 US FDA-approved drugs using six Web-tools - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Biopharmaceutics and Drug Disposition Année : 2021

Comparative in silico prediction of P-glycoprotein-mediated transport for 2010-2020 US FDA-approved drugs using six Web-tools

Résumé

P-glycoprotein (P-gp) is an efflux pump implicated in pharmacokinetics and drug-drug interactions. The identification of its substrates is consequently an important issue, notably for drugs under development. For such a purpose, various in silico methods have been developed, but their relevance remains to be fully established. The present study was designed to get insight about this point, through determining the performance values of six freely accessible Web-tools (ADMETlab, AdmetSAR2.0, PgpRules, pkCSM, SwissADME and vNN-ADMET), computationally predicting P-gp-mediated transport. Using an external test set of 231 marketed drugs, approved over the 2010-2020 period by the US Food and Drug Administration and fully in vitro characterized for their P-gp substrate status, various performance parameters (including sensitivity, specificity, accuracy, Matthews correlation coefficient and area under the receiver operating characteristics curve) were determined. They were found to rather poorly meet criteria commonly required for acceptable prediction, whatever the Web-tools were used alone or in combination. Predictions of being P-gp substrate or non-substrate by these online in silico methods may therefore be considered with caution.

Dates et versions

hal-03341369 , version 1 (10-09-2021)

Identifiants

Citer

Nelly Gueniche, Antoine Huguet, Arnaud Bruyere, Denis Habauzit, Ludovic Le Hegarat, et al.. Comparative in silico prediction of P-glycoprotein-mediated transport for 2010-2020 US FDA-approved drugs using six Web-tools. Biopharmaceutics and Drug Disposition, 2021, 42 (8), pp.393-398. ⟨10.1002/bdd.2299⟩. ⟨hal-03341369⟩
30 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More