title: The identification of AF38469: an orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin.
abstract: The identification of the novel, selective, orally bioavailable Sortilin inhibitor AF38469 is described. Structure-activity relationships and syntheses are reported, along with an X-ray crystal structure of the sortilin-AF38469 protein-inhibitor complex.
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Tenna Juul
authors.initials: TJ
authors.lastname: Schrøder
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Christensen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Samsa
authors.initials: S
authors.lastname: Lindberg
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Langgård
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Laurent
authors.initials: L
authors.lastname: David
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Maltas
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Eskildsen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Jacobsen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Tagmose
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Klaus Bæk
authors.initials: KB
authors.lastname: Simonsen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Biilmann Rønn
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Inge E M
authors.initials: IE
authors.lastname: de Jong
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Ibrahim J
authors.initials: IJ
authors.lastname: Malik
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Jens-Jakob
authors.initials: JJ
authors.lastname: Karlsson
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Bundgaard
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Egebjerg
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Stavenhagen
authors.affiliation: The Lundbeck Foundation Research Centre MIND, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, Aarhus C 8000, Denmark.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Strandbygård
authors.affiliation: The Lundbeck Foundation Research Centre MIND, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, Aarhus C 8000, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Thirup
authors.affiliation: The Lundbeck Foundation Research Centre MIND, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, Aarhus C 8000, Denmark.
authors.forename: Jacob Lauwring
authors.initials: JL
authors.lastname: Andersen
authors.affiliation: Medicinal Chemistry, GVK BioScience, Hyderabad, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Uppalanchi
authors.affiliation: Medicinal Chemistry, GVK BioScience, Hyderabad, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Pervaram
authors.affiliation: Medicinal Chemistry, GVK BioScience, Hyderabad, India.
authors.forename: Shiva Prasad
authors.initials: SP
authors.lastname: Kasturi
authors.affiliation: Medicinal Chemistry, GVK BioScience, Hyderabad, India.
authors.forename: Pradheep
authors.initials: P
authors.lastname: Eradi
authors.affiliation: Medicinal Chemistry, GVK BioScience, Hyderabad, India.
authors.forename: Durga Rao
authors.initials: DR
authors.lastname: Sakumudi
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark. Electronic address: stwa@lundbeck.com.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D006845:Hydrocarbons, Fluorinated; D011725:Pyridines; D000099183:Sortilin; C588336:AF38469
keywords: AF38469; AF40431; Neurotensin; Protein-inhibitor complex; Sortilin; Sortilin crystal structure; Sorting receptor; VPS10P