TY - JOUR T1 - GPCRs as targets for approved drugs: How many targets and how many drugs? JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.117.111062 SP - mol.117.111062 AU - Krishna Sriram AU - Paul A. Insel Y1 - 2018/01/01 UR - http://molpharm.aspetjournals.org/content/early/2018/01/03/mol.117.111062.abstract N2 - Estimates vary regarding the number of G protein-coupled receptors, GPCRs, the largest family of membrane receptors that are targeted by approved drugs and the number of such drugs that target GPCRs. We review current knowledge regarding GPCRs as drug targets by integrating data from public databases (CHEMBL, IUPHAR and DRUGBANK) and from the Broad drug repurposing initiative. To account for discrepancies among these sources, we curated a list of GPCRs currently targeted by approved drugs. As of November, 2017, 134 GPCRs are targets for drugs approved in the United States or European Union; 128 GPCRs are targets for drugs listed in the FDA orange book. We estimate that ~700 approved drugs target GPCRs, implying that approximately 35% of approved drugs target GPCRs. GPCRs and GPCR-related proteins, i.e. those upstream or downstream of GPCRs, represent ~17% of all protein targets for approved drugs, with GPCRs themselves accounting for ~12%. As such, GPCRs constitute the largest family of proteins targeted by approved drugs. Drugs that currently target GPCRs and GPCR related proteins are primarily small molecules and peptides. Since ~100 of the ~360 human endoGPCRs (other than olfactory, taste and visual GPCRs) are orphan receptors (lacking known physiologic agonists), the number of GPCR targets, the number of GPCR-targeted drugs and perhaps the types of drugs will likely increase, thus further expanding this GPCR repertoire and the many roles of GPCR-drugs in therapeutics. ER -