79
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Trends in GPCR drug discovery: new agents, targets and indications

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="P1">G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, largely due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report the first analysis of all GPCR drugs and agents in clinical trials. This reveals the current trends across molecule types, drug targets and therapeutic indications, including showing that 481 drugs (~34% of all drugs approved by the FDA) act at 107 unique GPCR targets. Approximately 320 agents are currently in clinical trials, of which ~36% target 64 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has grown. The major disease indications for GPCR modulators show a shift towards diabetes, obesity, and Alzheimer’s disease, while other central nervous system disorders remain highly represented. The 227 (57%) non-olfactory GPCRs that are yet to be explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug discovery. </p>

          Related collections

          Most cited references75

          • Record: found
          • Abstract: not found
          • Book: not found

          The operated Markov´s chains in economy (discrete chains of Markov with the income)

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            G protein pathways.

            The heterotrimeric guanine nucleotide-binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. The extracellular signals are received by members of a large superfamily of receptors with seven membrane-spanning regions that activate the G proteins, which route the signals to several distinct intracellular signaling pathways. These pathways interact with one another to form a network that regulates metabolic enzymes, ion channels, transporters, and other components of the cellular machinery controlling a broad range of cellular processes, including transcription, motility, contractility, and secretion. These cellular processes in turn regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Polypharmacology: challenges and opportunities in drug discovery.

              At present, the legendary magic bullet, i.e., a drug with high potency and selectivity toward a specific biological target, shares the spotlight with an emerging and alternative polypharmacology approach. Polypharmacology suggests that more effective drugs can be developed by specifically modulating multiple targets. It is generally thought that complex diseases such as cancer and central nervous system diseases may require complex therapeutic approaches. In this respect, a drug that "hits" multiple sensitive nodes belonging to a network of interacting targets offers the potential for higher efficacy and may limit drawbacks generally arising from the use of a single-target drug or a combination of multiple drugs. In this review, we will compare advantages and disadvantages of multitarget versus combination therapies, discuss potential drug promiscuity arising from off-target effects, comment on drug repurposing, and introduce approaches to the computational design of multitarget drugs.
                Bookmark

                Author and article information

                Journal
                Nature Reviews Drug Discovery
                Nat Rev Drug Discov
                Springer Science and Business Media LLC
                1474-1776
                1474-1784
                December 2017
                October 27 2017
                December 2017
                : 16
                : 12
                : 829-842
                Article
                10.1038/nrd.2017.178
                6882681
                29075003
                928ff2f3-b4ca-449c-9a2c-3c9641c1fa6e
                © 2017

                http://www.springer.com/tdm

                History

                Comments

                Comment on this article