Using quantitative systems pharmacology for novel drug discovery

Expert Opinion on Drug Discovery
Violeta I Pérez-Nueno

Abstract

Over the past three decades, the predominant paradigm in drug discovery was designing selective ligands for a specific target to avoid unwanted side effects. However, in the last 5 years, the aim has shifted to take into account the biological network in which they interact. Quantitative and Systems Pharmacology (QSP) is a new paradigm that aims to understand how drugs modulate cellular networks in space and time, in order to predict drug targets and their role in human pathophysiology. This review discusses existing computational and experimental QSP approaches such as polypharmacology techniques combined with systems biology information and considers the use of new tools and ideas in a wider 'systems-level' context in order to design new drugs with improved efficacy and fewer unwanted off-target effects. The use of network biology produces valuable information such as new indications for approved drugs, drug-drug interactions, proteins-drug side effects and pathways-gene associations. However, we are still far from the aim of QSP, both because of the huge effort needed to model precisely biological network models and the limited accuracy that we are able to reach with those. Hence, moving from 'one molecule for one target to ...Continue Reading

References

Jan 1, 1990·Methods in Enzymology·W R Pearson
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Nov 10, 2000·Lancet·I R Edwards, J K Aronson
Nov 10, 2001·Annual Review of Genomics and Human Genetics·T IdekerL Hood
Nov 17, 2001·JAMA : the Journal of the American Medical Association·K A PhillipsW Sadee
Feb 13, 2004·Bioinformatics·Jonathan D WrenHarold R Garner
Jan 6, 2005·Journal of the American Chemical Society·Jeffrey R HuthPhilip J Hajduk
Oct 6, 2005·Bioinformatics·Roland ArnoldWerner Mewes
Nov 12, 2005·Journal of Pharmacokinetics and Pharmacodynamics·Raymond MillerRichard L Lalonde
May 23, 2006·Journal of Chemical Information and Modeling· NidhiJeremy L Jenkins
Jul 15, 2006·Nature Biotechnology·Gaia V PaoliniAndrew L Hopkins
Jul 25, 2006·Journal of Chemical Information and Modeling·Elisabet Gregori-Puigjané, Jordi Mestres
Sep 26, 2006·Journal of Chemical Information and Modeling·Theodora M SteindlThierry Langer
Dec 13, 2006·Journal of Medicinal Chemistry·James H NettlesMeir Glick
Dec 28, 2006·Nature Protocols·Brian Y Feng, Brian K Shoichet
Feb 9, 2007·Nature Biotechnology·Michael J KeiserBrian K Shoichet
Mar 31, 2007·Journal of Molecular Graphics & Modelling·James H NettlesMeir Glick
Apr 27, 2007·Nature·Kathleen M GiacominiYusuke Nakamura
May 30, 2007·British Journal of Pharmacology·D Rognan
Jul 20, 2007·Assay and Drug Development Technologies·O V TrubetskoyV S Trubetskoy
Aug 10, 2007·Nature·Curtis R Chong, David J Sullivan
Oct 6, 2007·Nature Reviews. Drug Discovery·Georg C TerstappenGiovanni Gaviraghi
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Oleg FedorovStefan Knapp
Mar 14, 2008·Journal of Chemical Information and Modeling·Jérôme HertBrian K Shoichet
Jul 16, 2008·Science·Monica CampillosPeer Bork
Dec 6, 2008·Journal of Chemical Information and Modeling·Florian NigschJohn B O Mitchell
Feb 11, 2009·Nature Biotechnology·Irene NobeliJanet M Thornton
Apr 22, 2009·Journal of Medicinal Chemistry·Josef ScheiberJohn W Davies
May 13, 2009·Journal of Chemical Information and Modeling·Josef ScheiberJeremy L Jenkins
Sep 8, 2009·Current Opinion in Biotechnology·Peter KolbBrian K Shoichet
Sep 29, 2009·Journal of Chemical Information and Modeling·Anne Mai WassermannJürgen Bajorath
Oct 22, 2009·Journal of Chemical Information and Modeling·Laura Delgado-SolerJaime Rubio-Martinez
Nov 3, 2009·Nature·Michael J KeiserBryan L Roth
Feb 17, 2010·Database : the Journal of Biological Databases and Curation·K G DowellJ A Blake

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved