Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology.
Computational models of ADME-Tox
Computational models of disease
DILI
Drug development
Drug discovery
Drug repurposing
Induced pluripotent stem cells
Microphysiology systems
Omics analyses
PBPK
Personalized medicine
Quantitative systems pharmacology
Toxicology
Journal
Handbook of experimental pharmacology
ISSN: 0171-2004
Titre abrégé: Handb Exp Pharmacol
Pays: Germany
ID NLM: 7902231
Informations de publication
Date de publication:
2019
2019
Historique:
pubmed:
16
6
2019
medline:
22
1
2020
entrez:
16
6
2019
Statut:
ppublish
Résumé
Two technologies that have emerged in the last decade offer a new paradigm for modern pharmacology, as well as drug discovery and development. Quantitative systems pharmacology (QSP) is a complementary approach to traditional, target-centric pharmacology and drug discovery and is based on an iterative application of computational and systems biology methods with multiscale experimental methods, both of which include models of ADME-Tox and disease. QSP has emerged as a new approach due to the low efficiency of success in developing therapeutics based on the existing target-centric paradigm. Likewise, human microphysiology systems (MPS) are experimental models complementary to existing animal models and are based on the use of human primary cells, adult stem cells, and/or induced pluripotent stem cells (iPSCs) to mimic human tissues and organ functions/structures involved in disease and ADME-Tox. Human MPS experimental models have been developed to address the relatively low concordance of human disease and ADME-Tox with engineered, experimental animal models of disease. The integration of the QSP paradigm with the use of human MPS has the potential to enhance the process of drug discovery and development.
Identifiants
pubmed: 31201557
doi: 10.1007/164_2019_239
pmc: PMC6911651
mid: NIHMS1051498
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
327-367Subventions
Organisme : NCATS NIH HHS
ID : U01 TR002383
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103712
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117881
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA204826
Pays : United States
Organisme : NCATS NIH HHS
ID : U24 TR002632
Pays : United States
Organisme : NIDA NIH HHS
ID : P30 DA035778
Pays : United States
Organisme : NIDDK NIH HHS
ID : UG3 DK119973
Pays : United States
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