Cross-Pharmacology Analysis of G Protein-Coupled Receptors
| Autor: | Ferran Briansó, Jordi Mestres, Tudor I. Oprea, Maria C. Carrascosa |
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| Předmět: |
Protein family
Databases Factual Crosspharmacology signals Muscarinic receptors Genomics Pharmacology Biology Ligands Target profile Article Receptors G-Protein-Coupled GPCR-directed chemical libraries Similarity (network science) GPCR network Drug Discovery Humans Receptor G protein-coupled receptor Chemogenomic Databases Drug discovery Adverse effects Drug repositioning Cross-pharmacology analysis General Medicine Ligand (biochemistry) Small molecule Ligand similarity Pharmacological similarity Drug Design Clusters of non-GPCR targets |
| Zdroj: | ResearcherID |
| Popis: | The degree of applicability of chemogenomic approaches to protein families depends on the accuracy and completeness of pharmacological data and the corresponding level of pharmacological similarity observed among their protein members. The recent public domain availability of pharmacological data for thousands of small molecules on 204 G protein- coupled receptors (GPCRs) provides a firm basis for an in-depth cross-pharmacology analysis of this superfamily. The number of protein targets included in the cross-pharmacology profile of the different GPCRs changes significantly upon varying the ligand similarity and binding affinity criteria. However, with the exception of muscarinic receptors, aminergic GPCRs distinguish themselves from the rest of the members in the family by their remarkably high levels of pharmacological similarity among them. Clusters of non-GPCR targets related by cross-pharmacology with particular GPCRs are identified and the implications for unwanted side-effects, as well as for repurposing opportunities, discussed. This research was funded by the Instituto de Salud Carlos III, the Spanish Ministerio de Ciencia e Innovación (project reference BIO2008-02329) and the NIH grant 5U54MH084690-02. |
| Databáze: | OpenAIRE |
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