Experimental challenges to targeting poorly characterized GPCRs: uncovering the therapeutic potential for free fatty acid receptors.

摘要: The G protein-coupled receptors (GPCRs) are extremely successful drug targets, with recent estimates suggesting that approximately 30% of all currently available therapeutics act at these receptors. Despite this success, only a small number the over 400 known nonodorant GPCRs targeted, there is still untapped therapeutic potential. However, as most were identified based on their sequence homology to other members superfamily, many remain "orphan" without ligands. Indeed, even once GPCR has been deorphanized, receptor typically poorly characterized in terms its pharmacology and biological functions, presenting unique set experimental challenges order define We discuss some how they have addressed uncover potential five recently deorphanized activated by short- long-chain free fatty acids.