Title
Chemogenomics approaches for receptor deorphanization and extensions of the chemogenomics concept to phenotypic space
Author
van der Horst, E.
Peironcely, J.E.
van Westen, G.J.P.
van den Hoven, O.O.
Galloway, W.R.J.D.
Spring, D.R.
Wegner, J.K.
van Vlijmen, H.W.T.
Ijzerman, A.P.
Overington, J.P.
Bender, A.
Publication year
2011
Abstract
Chemogenomic approaches, which link ligand chemistry to bioactivity against targets (and, by extension, to phenotypes) are becoming more and more important due to the increasing number of bioactivity data available both in proprietary databases as well as in the public domain. In this article we review chemogenomics approaches applied in four different domains: Firstly, due to the relationship between protein targets from which an approximate relation between their respective bioactive ligands can be inferred, we investigate the extent to which chemogenomics approaches can be applied to receptor deorphanization. In this case it was found that by using knowledge about active compounds of related proteins, in 93% of all cases enrichment better than random could be obtained. Secondly, we analyze different chemin-formatics analysis methods with respect to their behavior in chemogenomics studies, such as subgraph mining and Baye-sian models. Thirdly, we illustrate how chemogenomics, in its particular flavor of 'proteochemometrics', can be applied to extrapolate bioactivity predictions from given data points to related targets. Finally, we extend the concept of 'chemoge-nomics' approaches, relating ligand chemistry to bioactivity against related targets, into phenotypic space which then falls into the area of 'chemical genomics' and 'chemical genetics'; given that this is very often the desired endpoint of approaches in not only the pharmaceutical industry, but also in academic probe discovery, this is often the endpoint the experimental scientist is most interested in. © 2011 Bentham Science Publishers.
Subject
Life
QS - Quality & Safety
EELS - Earth, Environmental and Life Sciences
Healthy for Life
Nutrition
Healthy Living
Chemogenomics
Deorphanization
G-protein coupled receptors
GPCR
Mode of action analysis
Orphan receptors
Proteochemometrics
Target prediction
Virtual screening
G protein coupled receptor
ligand
Bayes theorem
chemical genetics
chemistry
chemogenomic
drug activity
drug industry
genomics
phenotype
proteochemometrics
review
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http://resolver.tudelft.nl/uuid:a1c1df37-349f-4af2-9916-1a55fc17c44e
DOI
https://doi.org/10.2174/156802611796391230
TNO identifier
434667
ISSN
1568-0266
Source
Current Topics in Medicinal Chemistry, 11 (15), 1964-1977
Document type
article