Toward in vivo relevant drug design.
Journal
Drug discovery today
ISSN: 1878-5832
Titre abrégé: Drug Discov Today
Pays: England
ID NLM: 9604391
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
04
03
2020
revised:
16
09
2020
accepted:
15
10
2020
pubmed:
3
11
2020
medline:
12
1
2022
entrez:
2
11
2020
Statut:
ppublish
Résumé
Current early and preclinical drug discovery are rooted in decades-old empirical principles describing structure-free energy and structure-function relationships under equilibrium conditions that frequently break down under in vivo conditions. Improved prediction of efficacy and toxicity depends on a paradigm shift to in vivo-relevant principles describing the true nonequilibrium/nonlinear dynamic (NLD) nature of cellular systems. Here, we outline a holistic, in vivo-relevant first principles theory ('Biodynamics'), in which cellular function/dysfunction, and pharmaco-/toxicodynamic effects are considered as emergent behaviors of multimolecular systems powered by covalent and noncovalent free energy sources. The reduction to practice of Biodynamics theory consists of in silico simulations performed at the atomistic and molecular systems levels, versus empirical models fit to in vitro data under the classical paradigm.
Identifiants
pubmed: 33132106
pii: S1359-6446(20)30429-3
doi: 10.1016/j.drudis.2020.10.012
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
637-650Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.