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Small molecule inhibitors of regulators of G protein signaling (RGS) proteins


Reference:

Turner, E. M., Blazer, L. L., Neubig, R. R. and Husbands, S. M., 2012. Small molecule inhibitors of regulators of G protein signaling (RGS) proteins. ACS Medicinal Chemistry Letters, 3 (2), pp. 146-150.

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    Official URL:

    http://dx.doi.org/10.1021/ml200263y

    Abstract

    Recently, regulators of G protein signaling (RGS) proteins have emerged as potential therapeutic targets since they provide an alternative method of modulating the activity of G protein-coupled receptors, the target of so many drugs. Inhibitors of RGS proteins must block a protein protein interaction (RGS-G alpha) but also be cell and, depending on the therapeutic target, blood brain barrier permeable. A lead compound (la) was identified as an inhibitor of RGS4 in a screening assay, and this has now been optimized for activity, selectivity, and solubility. The newly developed ligands (11b and 13) display substantial selectivity over the closely related RGS8 protein, lack the off-target calcium mobilization activity of the lead la, and have excellent aqueous solubility. They are currently being evaluated in vivo in rodent models of depression.

    Details

    Item Type Articles
    CreatorsTurner, E. M., Blazer, L. L., Neubig, R. R. and Husbands, S. M.
    DOI10.1021/ml200263y
    DepartmentsFaculty of Science > Pharmacy & Pharmacology
    Publisher StatementHusbands_ACSMCL_2012_3_2_146.pdf: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/ml200263y; Husbands_ACSMCL_2012_3_2_146.docx: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/ml200263y
    RefereedYes
    StatusPublished
    ID Code29167

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