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
TLDR
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.Abstract:
The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development. Here, we present an updated comprehensive map of molecular targets of approved drugs. We curate a total of 893 human and pathogen-derived biomolecules through which 1,578 US FDA-approved drugs act. These biomolecules include 667 human-genome-derived proteins targeted by drugs for human disease. Analysis of these drug targets indicates the continued dominance of privileged target families across disease areas, but also the growth of novel first-in-class mechanisms, particularly in oncology. We explore 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. Through the collaboration of three independent teams, we highlight some of the ongoing challenges in accurately defining the targets of molecular therapeutics and present conventions for deconvoluting the complexities of molecular pharmacology and drug efficacy.read more
Citations
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Trends in GPCR drug discovery: new agents, targets and indications
Alexander S. Hauser,Misty M. Attwood,Mathias Rask-Andersen,Helgi B. Schiöth,David E. Gloriam +4 more
TL;DR: An up-to-date analysis of all GPCR drugs and agents in clinical trials is reported, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs act at 108 unique GPCRs.
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Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
Yadi Zhou,Yuan Hou,Jiayu Shen,Yin Huang,William R. Martin,Feixiong Cheng,Feixiong Cheng,Feixiong Cheng +7 more
TL;DR: This study presents an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network.
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G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?
Krishna Sriram,Paul A. Insel +1 more
TL;DR: 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.
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Opportunities and challenges in phenotypic drug discovery: an industry perspective
TL;DR: This article focuses on the lessons learned by researchers engaged in PDD in the pharmaceutical industry and considers the impact of 'omics' knowledge in defining a cellular disease phenotype in the era of precision medicine, introducing the concept of a chain of translatability.
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Next generation antibody drugs: pursuit of the 'high-hanging fruit'.
Paul Carter,Greg A. Lazar +1 more
TL;DR: This Review focuses on emerging and novel mechanisms of action of antibodies and innovative targeting strategies that could extend their therapeutic applications, including antibody–drug conjugates, bispecific antibodies and antibody engineering to facilitate more effective delivery.
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