Research ArticleArticle
Open Access
Bitopic Binding Mode of an M1 Muscarinic Acetylcholine Receptor Agonist Associated with Adverse Clinical Trial Outcomes
Sophie J. Bradley, Colin Molloy, Christoffer Bundgaard, Adrian J. Mogg, Karen J. Thompson, Louis Dwomoh, Helen E. Sanger, Michael D. Crabtree, Simon M. Brooke, Patrick M. Sexton, Christian C. Felder, Arthur Christopoulos, Lisa M. Broad, Andrew B. Tobin and Christopher J. Langmead
Molecular Pharmacology June 2018, 93 (6) 645-656; DOI: https://doi.org/10.1124/mol.118.111872
Sophie J. Bradley
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Colin Molloy
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Christoffer Bundgaard
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Adrian J. Mogg
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Karen J. Thompson
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Louis Dwomoh
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Helen E. Sanger
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Michael D. Crabtree
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Simon M. Brooke
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Patrick M. Sexton
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Christian C. Felder
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Arthur Christopoulos
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Lisa M. Broad
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Andrew B. Tobin
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
Christopher J. Langmead
The Centre for Translational Pharmacology, Institute of Molecular, Cell, and Systems Biology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland (S.J.B., C.M., K.J.T., L.D., S.M.B., A.B.T.); Eli Lilly & Co. Neuroscience, Windlesham, Surrey, United Kingdom (C.B., A.J.M., H.E.S., M.D.C., L.M.B.); Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (P.M.S., A.C., C.J.L.); and Eli Lilly & Co. Neuroscience, Indianapolis, Indiana (C.C.F.)
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Research ArticleArticle
Novel Bitopic Mode of an M1 Agonist
Sophie J. Bradley, Colin Molloy, Christoffer Bundgaard, Adrian J. Mogg, Karen J. Thompson, Louis Dwomoh, Helen E. Sanger, Michael D. Crabtree, Simon M. Brooke, Patrick M. Sexton, Christian C. Felder, Arthur Christopoulos, Lisa M. Broad, Andrew B. Tobin and Christopher J. Langmead
Molecular Pharmacology June 1, 2018, 93 (6) 645-656; DOI: https://doi.org/10.1124/mol.118.111872
Research ArticleArticle
Novel Bitopic Mode of an M1 Agonist
Sophie J. Bradley, Colin Molloy, Christoffer Bundgaard, Adrian J. Mogg, Karen J. Thompson, Louis Dwomoh, Helen E. Sanger, Michael D. Crabtree, Simon M. Brooke, Patrick M. Sexton, Christian C. Felder, Arthur Christopoulos, Lisa M. Broad, Andrew B. Tobin and Christopher J. Langmead
Molecular Pharmacology June 1, 2018, 93 (6) 645-656; DOI: https://doi.org/10.1124/mol.118.111872
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