Publication Date:
2019
Description:
〈p〉Publication date: Available online 9 August 2019〈/p〉
〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry Letters〈/p〉
〈p〉Author(s): Alistair O'Brien, Steve Andrews, Asma H. Baig, Andrea Bortolato, Alastair J.H. Brown, Giles A. Brown, Sue H. Brown, John A. Christopher, Miles Congreve, Robert M. Cooke, Chris De Graaf, James C. Errey, Charlotte Fieldhouse, Ali Jazayeri, Fiona H. Marshall, Jonathan S. Mason, Juan Carlos Mobarec, Krzysztof Okrasa, Kelly N. Steele, Stacey M. Southall〈/p〉
〈div xml:lang="en"〉
〈h5〉Abstract〈/h5〉
〈div〉〈p〉A series of novel allosteric antagonists of the GLP-1 receptor (GLP-1R), exemplified by HTL26119, are described. SBDD approaches were employed to identify HTL26119, exploiting structural understanding of the allosteric binding site of the closely related Glucagon receptor (GCGR) (Jazayeri et al., 2016) and the homology relationships between GCGR and GLP-1R. The region around residue C347〈sup〉6.36b〈/sup〉 of the GLP-1R receptor represents a key difference from GCGR and was targeted for selectivity for GLP-1R.〈/p〉〈/div〉
〈/div〉
〈div xml:lang="en"〉
〈h5〉Graphical abstract〈/h5〉
〈div〉〈p〉A series of novel allosteric antagonists of the GLP-1 receptor (GLP-1R), exemplified by HTL26119, are described.〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0960894X19305426-ga1.jpg" width="298" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉
〈/div〉
Print ISSN:
0960-894X
Electronic ISSN:
1464-3405
Topics:
Chemistry and Pharmacology
,
Medicine
Permalink