The identification of AF38469: an orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin

  • Bioorg Med Chem Lett. 2014 Jan 1;24(1):177-80. doi: 10.1016/j.bmcl.2013.11.046.
Tenna Juul Schrøder  1 ,  Søren Christensen  1 ,  Samsa Lindberg  1 ,  Morten Langgård  1 ,  Laurent David  1 ,  Philip J Maltas  1 ,  Jørgen Eskildsen  1 ,  Jan Jacobsen  1 ,  Lena Tagmose  1 ,  Klaus Bæk Simonsen  1 ,  Lars Christian Biilmann Rønn  1 ,  Inge E M de Jong  1 ,  Ibrahim J Malik  1 ,  Jens-Jakob Karlsson  1 ,  Christoffer Bundgaard  1 ,  Jan Egebjerg  1 ,  Jeffrey B Stavenhagen  1 ,  Dorthe Strandbygård  2 ,  Søren Thirup  2 ,  Jacob Lauwring Andersen  2 ,  Srinivas Uppalanchi  3 ,  Sridhar Pervaram  3 ,  Shiva Prasad Kasturi  3 ,  Pradheep Eradi  3 ,  Durga Rao Sakumudi  3 ,  Stephen P Watson  4
Affiliations
  • 1. Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark.
  • 2. The Lundbeck Foundation Research Centre MIND, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, Aarhus C 8000, Denmark.
  • 3. Medicinal Chemistry, GVK BioScience, Hyderabad, India.
  • 4. Neuroscience Drug Discovery, H. Lundbeck A/S, Copenhagen, Denmark. Electronic address: [email protected].
PMID: 24355129 DOI: 10.1016/j.bmcl.2013.11.046
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.

Keywords
AF38469; AF40431; Neurotensin; Protein-inhibitor complex; Sortilin; Sortilin crystal structure; Sorting receptor; VPS10P.
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