G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?
Krishna Sriram,Paul A. Insel +1 more
Reads0
Chats0
TLDR
A list of GPCRs currently targeted by approved drugs is curated by integrating data from public databases and from the Broad Institute Drug Repurposing Hub to account for discrepancies among these sources.Abstract:
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, Guide to PHARMACOLOGY, and DrugBank) and from the Broad Institute Drug Repurposing Hub. 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 Food and Drug Administration 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 of or downstream from 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 endo-GPCRs (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.read more
Citations
More filters
Journal ArticleDOI
Mechanisms of signalling and biased agonism in G protein-coupled receptors
Denise Wootten,Arthur Christopoulos,Maria Marti-Solano,M. Madan Babu,Patrick M. Sexton,Patrick M. Sexton +5 more
TL;DR: Increasing molecular and structural understanding of biased agonism offers the possibility of designing improved GPCR-targeting drugs, and refined classification of drugs according to their pharmacodynamic profiles, which can be linked to receptor structure and predictions of preclinical drug efficacy.
Journal ArticleDOI
G protein-coupled receptors: structure- and function-based drug discovery.
Dehua Yang,Qingtong Zhou,Viktorija Labroska,Shanshan Qin,Sanaz Darbalaei,Yiran Wu,Elita Yuliantie,Linshan Xie,Houchao Tao,Jianjun Cheng,Qing Liu,Suwen Zhao,Wenqing Shui,Yi Jiang,Ming-Wei Wang +14 more
TL;DR: A comprehensive overview of the field of G protein-coupled receptors (GPCRs) can be found in this article, where the authors provide a broader readership that shares some common interests in drug discovery.
Journal ArticleDOI
Directed Evolution: Methodologies and Applications.
TL;DR: Directed evolution aims to expedite the natural evolution process of biological molecules and systems in a test tube through iterative rounds of gene diversifications and library screening/selection.
Journal ArticleDOI
SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation.
David W. Sanders,Chanelle C. Jumper,Paul J Ackerman,Dan Bracha,Anita Donlic,Hahn Kim,Devin Kenney,Ivan Castello-Serrano,Saori Suzuki,Tomokazu Tamura,Alexander H Tavares,Mohsan Saeed,Alex S. Holehouse,Alexander Ploss,Ilya Levental,Florian Douam,Robert F. Padera,Bruce D. Levy,Clifford P. Brangwynne,Clifford P. Brangwynne +19 more
TL;DR: In this paper, the authors report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those identified in lungs of COVID-19 patients.
Journal ArticleDOI
Peptide-Drug Conjugates and Their Targets in Advanced Cancer Therapies.
TL;DR: In this review, the benefits of peptides as tumor homing agents are presented and an overview of the most commonly addressed peptide receptors is given and a special focus was set on the bombesin receptor family and the neuropeptide Y receptor family.
References
More filters
Journal ArticleDOI
UniProt: the Universal Protein knowledgebase
Rolf Apweiler,Amos Marc Bairoch,Cathy H. Wu,Winona C. Barker,Brigitte Boeckmann,Serenella Ferro,Elisabeth Gasteiger,Hongzhan Huang,Rodrigo Lopez,Michele Magrane,Maria Jesus Martin,Darren A. Natale,Claire O'Donovan,Nicole Redaschi,Lai-Su L. Yeh +14 more
TL;DR: The Swiss-Prot, TrEMBL and PIR protein database activities have united to form the Universal Protein Knowledgebase (UniProt), which is to provide a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and query interfaces.
Journal ArticleDOI
DrugBank: a knowledgebase for drugs, drug actions and drug targets
David S. Wishart,Craig Knox,An Chi Guo,Dean Cheng,Savita Shrivastava,Dan Tzur,Bijaya Gautam,Murtaza Hassanali +7 more
TL;DR: The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release and contains 60% more FDA-approved small molecule and biotech drugs including 10% more ‘experimental’ drugs.
Journal ArticleDOI
A comprehensive map of molecular drug targets
Rita Santos,Rita Santos,Oleg Ursu,Anna Gaulton,A. Patrícia Bento,Ramesh S. Donadi,Cristian Bologa,Anneli Karlsson,Bissan Al-Lazikani,Anne Hersey,Tudor I. Oprea,John P. Overington +11 more
TL;DR: An updated comprehensive map of molecular targets of approved drugs is presented and the relationships between bioactivity class and clinical success, as well as the presence of orthologues between human and animal models and between pathogen and human genomes are explored.
Journal ArticleDOI
The ChEMBL bioactivity database: an update
A. Patrícia Bento,Anna Gaulton,Anne Hersey,Louisa J. Bellis,Jon Chambers,Mark Davies,Felix A. Kruger,Yvonne Light,Lora Mak,Shaun McGlinchey,Michal Nowotka,George Papadatos,Rita Santos,John P. Overington +13 more
TL;DR: More comprehensive tracking of compounds from research stages through clinical development to market is provided through the inclusion of data from United States Adopted Name applications and a new richer data model for representing drug targets has been developed.
Journal ArticleDOI
The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands
Christopher Southan,Joanna L. Sharman,Helen E. Benson,Elena Faccenda,Adam J. Pawson,Stephen P.H. Alexander,Peter Buneman,Anthony P. Davenport,John C. McGrath,John C. McGrath,John A. Peters,Michael Spedding,William A. Catterall,Doriano Fabbro,Jamie A. Davies +14 more
TL;DR: The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) database provides expert-curated molecular interactions between successful and potential drugs and their targets in the human genome, and provides an expanded substrate for the biennially published compendium, the Concise Guide topharmacology.
Related Papers (5)
The structure and function of G-protein-coupled receptors
Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Søren G. F. Rasmussen,Brian T. DeVree,Yaozhong Zou,Andrew C. Kruse,Ka Young Chung,Tong Sun Kobilka,Foon Sun Thian,Pil Seok Chae,Els Pardon,Els Pardon,Diane M. Calinski,Jesper Mosolff Mathiesen,Syed T. A. Shah,Joseph A. Lyons,Martin Caffrey,Samuel H. Gellman,Jan Steyaert,Jan Steyaert,Georgios Skiniotis,William I. Weis,Roger K. Sunahara,Brian K. Kobilka +21 more