Emergence of small molecule non-RGD-mimetic inhibitors for RGD integrins

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Miller, Lisa M. and Pritchard, John M. and Macdonald, Simon J. F. and Jamieson, Craig and Watson, Allan J. B. (2017) Emergence of small molecule non-RGD-mimetic inhibitors for RGD integrins. Journal of Medicinal Chemistry, 60 (8). ISSN 0022-2623 (https://doi.org/10.1021/acs.jmedchem.6b01711)

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Abstract

The RGD integrins are recognized therapeutic targets for thrombosis, fibrosis, and cancer, amongst others. Current inhibitors are designed to mimic the tripeptide sequence (arginineglycine-aspartic acid) of the natural ligands; however, the RGD-mimetic antagonists for αIIbβ3 have been shown to cause partial agonism, leading to the opposite pharmacological effect. The challenge of obtaining oral activity and synthetic tractability with RGD-mimetic molecules, along with the issues relating to pharmacology, has left integrin-therapeutics in need of a new strategy. Recently, a new generation of inhibitor has emerged that lacks the RGD-mimetic. This 2 perspective will discuss the discovery of these non-RGD-mimetic inhibitors, and the progress that has been made in this promising new chemotype.

ORCID iDs

Miller, Lisa M. ORCID logoORCID: https://orcid.org/0000-0002-0378-1071, Pritchard, John M., Macdonald, Simon J. F., Jamieson, Craig ORCID logoORCID: https://orcid.org/0000-0002-6567-8272 and Watson, Allan J. B.;
  • Item type:Article
    ID code:60317
    Dates:
    Date
    Event
    30 January 2017
    Published
    30 January 2017
    Published Online
    22 November 2016
    Accepted
    Notes:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jmedchem.6b01711
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Strategic Research Themes > Health and Wellbeing
    Depositing user: Pure Administrator
    Date deposited:27 Mar 2017 15:44
    Last modified:15 Dec 2024 01:23
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/60317
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