THE HIDDEN PHARMACOLOGY OF THE HUMAN GPCR-OME

摘要

My view of the present state of research on GPCR drug discovery With nearly 900 members, the human GPCR-ome comprises the largest family of druggable targets in the genome although most members have not been chemically interrogated. G protein-coupled receptors(GPCRs)constitute the single largest class of druggable targets in the human genome [1]. The human genome includes genes for~900 olfactory and non-olfactory GPCRs and careful analyses estimate the number of non-olfactory GPCRs to be between 342 and 356(http://www.iuphardb.org/index.jsp)[2]. Of these, approximately 38% are classified as "orphans", i.e.,their natural(endogenous)ligands remain unknown(see IUPHAR GPCR Database at: http://www.iuphar-db.org/index.jsp). Additionally a significant proportion of the non-orphan GPCRs remain incompletely or inaccurately characterized with respect to the ligands that modulate their activity.