Phenotypic screening in the 21st century
In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and th...
- Autores:
- Tipo de recurso:
- Book
- Fecha de publicación:
- 2015
- Institución:
- Universidad de Bogotá Jorge Tadeo Lozano
- Repositorio:
- Expeditio: repositorio UTadeo
- Idioma:
- eng
- OAI Identifier:
- oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/14277
- Acceso en línea:
- https://www.frontiersin.org/research-topics/1725/phenotypic-screening-in-the-21st-century
http://hdl.handle.net/20.500.12010/14277
- Palabra clave:
- Therapeutics
Science (General)
Label-free technologies
Phenotypic screenning
Target-based assays
Systems Biology
Pathways
Drug Discovery
Panomic data
Gene networks ---
- Rights
- License
- Abierto (Texto Completo)
id |
UTADEO2_2bcc75a102afb1096038c73e741f2b11 |
---|---|
oai_identifier_str |
oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/14277 |
network_acronym_str |
UTADEO2 |
network_name_str |
Expeditio: repositorio UTadeo |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Phenotypic screening in the 21st century |
title |
Phenotypic screening in the 21st century |
spellingShingle |
Phenotypic screening in the 21st century Therapeutics Science (General) Label-free technologies Phenotypic screenning Target-based assays Systems Biology Pathways Drug Discovery Panomic data Gene networks --- |
title_short |
Phenotypic screening in the 21st century |
title_full |
Phenotypic screening in the 21st century |
title_fullStr |
Phenotypic screening in the 21st century |
title_full_unstemmed |
Phenotypic screening in the 21st century |
title_sort |
Phenotypic screening in the 21st century |
dc.subject.spa.fl_str_mv |
Therapeutics Science (General) Label-free technologies |
topic |
Therapeutics Science (General) Label-free technologies Phenotypic screenning Target-based assays Systems Biology Pathways Drug Discovery Panomic data Gene networks --- |
dc.subject.lemb.spa.fl_str_mv |
Phenotypic screenning Target-based assays Systems Biology Pathways |
dc.subject.keyword.spa.fl_str_mv |
Drug Discovery Panomic data Gene networks --- |
description |
In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and the suitability of target-based drug discovery as an optimal strategy for all disease states. For monogenic diseases, target-based approaches may be well-suited to the identification of novel therapies. Most diseases, however, are caused by a combination of several genetic and environmental factors and are likely to require simultaneous modulation of multiple molecular targets/pathways for successful treatment. For such diseases, reductionist approaches focusing on individual targets rather than biological networks are unlikely to succeed and new drug development strategies are required. In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and systems biology perspective. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigour. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style. This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include: • The need for systems-based approaches in drug development • Phenotypic screening strategies • Compound libraries (natural product inspired compound collections) • Target deconvolution and identification • Target agnostic lead discovery and optimization • Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modelling) • Translational aspects • Early evaluation of selectivity and safety in a target agnostic manner. |
publishDate |
2015 |
dc.date.created.none.fl_str_mv |
2015 |
dc.date.accessioned.none.fl_str_mv |
2020-10-06T20:27:02Z |
dc.date.available.none.fl_str_mv |
2020-10-06T20:27:02Z |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2f33 |
format |
http://purl.org/coar/resource_type/c_2f33 |
dc.identifier.isbn.none.fl_str_mv |
978-2-88919-469-8 |
dc.identifier.issn.none.fl_str_mv |
1664-8714 |
dc.identifier.other.none.fl_str_mv |
https://www.frontiersin.org/research-topics/1725/phenotypic-screening-in-the-21st-century |
dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/20.500.12010/14277 |
dc.identifier.doi.none.fl_str_mv |
10.3389/978-2-88919-469-8 |
identifier_str_mv |
978-2-88919-469-8 1664-8714 10.3389/978-2-88919-469-8 |
url |
https://www.frontiersin.org/research-topics/1725/phenotypic-screening-in-the-21st-century http://hdl.handle.net/20.500.12010/14277 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.references.none.fl_str_mv |
Priest BT and Erdemli G (2014) Phenotypic screening in the 21st century. doi: 10.3389/fphar.2014.00264 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.local.spa.fl_str_mv |
Abierto (Texto Completo) |
dc.rights.creativecommons.none.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
rights_invalid_str_mv |
Abierto (Texto Completo) https://creativecommons.org/licenses/by/4.0/ http://purl.org/coar/access_right/c_abf2 |
dc.format.extent.spa.fl_str_mv |
68 páginas |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
Frontiers Media SA |
institution |
Universidad de Bogotá Jorge Tadeo Lozano |
bitstream.url.fl_str_mv |
https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14277/1/Phenotypic%20screening%20in%20the%2021st%20century.PDF https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14277/2/license.txt https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14277/3/Phenotypic%20screening%20in%20the%2021st%20century.PDF.jpg |
bitstream.checksum.fl_str_mv |
d01c2e5acc82554fca76b24b0a859cbd abceeb1c943c50d3343516f9dbfc110f e50a7ef3e1dcff75994bf6309324cb08 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional - Universidad Jorge Tadeo Lozano |
repository.mail.fl_str_mv |
expeditio@utadeo.edu.co |
_version_ |
1814213497392726016 |
spelling |
2020-10-06T20:27:02Z2020-10-06T20:27:02Z2015978-2-88919-469-81664-8714https://www.frontiersin.org/research-topics/1725/phenotypic-screening-in-the-21st-centuryhttp://hdl.handle.net/20.500.12010/1427710.3389/978-2-88919-469-868 páginasapplication/pdfengFrontiers Media SATherapeuticsScience (General)Label-free technologiesPhenotypic screenningTarget-based assaysSystems BiologyPathwaysDrug DiscoveryPanomic dataGene networks ---Phenotypic screening in the 21st centuryAbierto (Texto Completo)https://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2Priest BT and Erdemli G (2014) Phenotypic screening in the 21st century. doi: 10.3389/fphar.2014.00264In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and the suitability of target-based drug discovery as an optimal strategy for all disease states. For monogenic diseases, target-based approaches may be well-suited to the identification of novel therapies. Most diseases, however, are caused by a combination of several genetic and environmental factors and are likely to require simultaneous modulation of multiple molecular targets/pathways for successful treatment. For such diseases, reductionist approaches focusing on individual targets rather than biological networks are unlikely to succeed and new drug development strategies are required. In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and systems biology perspective. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigour. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style. This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include: • The need for systems-based approaches in drug development • Phenotypic screening strategies • Compound libraries (natural product inspired compound collections) • Target deconvolution and identification • Target agnostic lead discovery and optimization • Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modelling) • Translational aspects • Early evaluation of selectivity and safety in a target agnostic manner.http://purl.org/coar/resource_type/c_2f33Erdemli, GulPriest, Birgit T.ORIGINALPhenotypic screening in the 21st century.PDFPhenotypic screening in the 21st century.PDFVer documentoapplication/pdf6062378https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14277/1/Phenotypic%20screening%20in%20the%2021st%20century.PDFd01c2e5acc82554fca76b24b0a859cbdMD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-82938https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14277/2/license.txtabceeb1c943c50d3343516f9dbfc110fMD52open accessTHUMBNAILPhenotypic screening in the 21st century.PDF.jpgPhenotypic screening in the 21st century.PDF.jpgIM Thumbnailimage/jpeg19649https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/14277/3/Phenotypic%20screening%20in%20the%2021st%20century.PDF.jpge50a7ef3e1dcff75994bf6309324cb08MD53open access20.500.12010/14277oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/142772021-02-22 19:22:06.219open accessRepositorio Institucional - Universidad Jorge Tadeo Lozanoexpeditio@utadeo.edu.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 |