1352552-35-2Relevant academic research and scientific papers
SMALL MOLECULE INHIBITORS OF RGS PROTEINS
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Page/Page column 24; 29, (2012/11/08)
The invention relates to compositions having RGS (regulator of G-protein Signaling) inhibiting activity, and methods of use thereof. In some embodiments, RGS-inhibiting compositions find use in research on or treatment of disease states (e.g., diabetes, epilepsy, neuropathic pain, depression and other diseases)
Small molecule inhibitors of regulators of G protein signaling (rgs) proteins
Turner, Emma M.,Blazer, Levi L.,Neubig, Richard R.,Husbands, Stephen M.
supporting information; experimental part, p. 146 - 150 (2012/04/04)
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-Gα) but also be cell and, depending on the therapeutic target, blood-brain barrier permeable. A lead compound (1a) 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 1a, and have excellent aqueous solubility. They are currently being evaluated in vivo in rodent models of depression.
