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Established and In-trail GPCR Families in Clinical Trials: A Review for Target Selection


Surovi Saikia, Manobjyoti Bordoloi* and Rajeev Sarmah   Pages 1 - 15 ( 15 )


The largest family of drug targets in clinical trials constitute of GPCRs (G-protein coupled receptors) which accounts for about 34% of FDA (Food and Drug Administration) approved drugs acting on 108 unique GPCRs. Factors such as readily identifiable conserved motif in structures, 127 orphan GPCRs despite various de-orphaning techniques, directed functional antibodies for validation as drug targets etc. has widened their therapeutic window. The availability of 44 crystal structures of unique receptors, unexplored non-olfactory GPCRs (encoded by 50% of the human genome) and 205 ligand-receptor complexes now present a strong foundation for structure-based drug discovery and design. The growing impact of polypharmacology for complex diseases like schizophrenia, cancer etc. warrants the need for novel targets and considering the undiscriminating and selectivity of GPCRs, they can fulfill this purpose. Again, natural genetic variations within the human genome sometimes delude the therapeutic expectations of some drugs, resulting in medication response differences and ADRs (adverse drug reactions). Around ~30 billion US dollars are dumped annually for a poor accounting of ADRs in the US alone. To curb such undesirable reactions, the knowledge of established and currently in clinical trials GPCRs families can offer a huge understanding of the drug designing prospects including “off-target” effects reducing economical resource and time. The druggability of GPCR protein families and critical roles played by them in complex diseases are explained. Class A, class B1, class C and class F are generally established family and GPCRs in phase I (19%), phase II(29%), phase III(52%) studies are also reviewed. From the phase I studies, frizzled receptors accounted for the highest in trial targets, neuropeptides in phase II and melanocortin in phase III studies. Also, the bioapplications for nanoparticles along with future prospects for both nanomedicine and GPCR drug industry are discussed.


G-protein coupled receptors, drug target, clinical trials, receptor proteins, drug discovery, disease


Natural Products Chemistry Group, CSIR North East Institute of Science & Technology, Jorhat-785006, Assam, Natural Products Chemistry Group, CSIR North East Institute of Science & Technology, Jorhat-785006, Assam, Allied Health Sciences, Assam Down Town University, Panikhaiti, Guwahati 781026, Assam

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