作者: Gregory Stewart , Julie Kniazeff , Laurent Przeau , Philippe Rondard , Jean-Philippe Pin
DOI: 10.5772/32481
关键词:
摘要: G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and due to their ubiquitous expression vast array functions they present attractive targets for treatment a wide number diseases disorders. Accordingly, represent up 30% current therapeutics (Overington et al., 2006). Despite capacity GPCRs modulate many (patho-)physiological there is high attrition rate with regard new compounds entering clinical trials. There reasons failed drug-like such as non-specificity, unfavourable pharmacokinetic profile lack efficacy. In this regard, molecules targeting neurotransmitter in CNS traditionally have poor side-effect profiles concentrations required pass blood-brain barrier. remain specific challenges drug discovery promiscuous GPCR-effector coupling; differential celland tissue-specific effects; ligand-induced changes receptor trafficking; proteinprotein interactions oligomerisation (Galandrin 2007; Hanyaloglu von Zastrow, 2008; Kniazeff 2011; Wettschureck Offermanns, 2005).