2. Academic Validation
  3. Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists

Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists

  • Sci Rep. 2016 Aug 16;6:30859. doi: 10.1038/srep30859.
Shenping Liu 1,  Leslie A Dakin 2,  Li Xing 2,  Jane M Withka 1,  Parag V Sahasrabudhe 1,  Wei Li 3,  Mary Ellen Banker 4,  Paul Balbo 3,  Suman Shanker 1,  Boris A Chrunyk 1,  Zuojun Guo 2,  Jinshan M Chen 1,  Jennifer A Young 1,  Guoyun Bai 1,  Jeremy T Starr 1,  Stephen W Wright 1,  Joerg Bussenius 5,  Sheng Tan 5,  Ariamala Gopalsamy 2,  Bruce A Lefker 2,  Fabien Vincent 4,  Lyn H Jones 2,  Hua Xu 2,  Lise R Hoth 1,  Kieran F Geoghegan 1,  Xiayang Qiu 1,  Mark E Bunnage 2,  Atli Thorarensen 2
Affiliations

Affiliations

  • 1 Worldwide Medicinal Chemistry, Pfizer Worldwide R&D, Eastern Point Road, Groton, CT 06340, USA.
  • 2 Worldwide Medicinal Chemistry, Pfizer Worldwide R&D, 610 Main Street, Cambridge, MA 02139, USA.
  • 3 Inflammation and Immunoscience Research Unit, Pfizer Worldwide R&D, 610 Main Street, Cambridge, MA 02139, USA.
  • 4 Primary Pharmacology Group, Pfizer Worldwide R&D, Eastern Point Road, Groton, CT 06340, USA.
  • 5 WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
PMID: 27527709 DOI: 10.1038/srep30859
Abstract

Interleukin-17A (IL-17A) is a principal driver of multiple inflammatory and immune disorders. Antibodies that neutralize IL-17A or its receptor (IL-17RA) deliver efficacy in autoimmune diseases, but no small-molecule IL-17A antagonists have yet progressed into clinical trials. Investigation of a series of linear peptide ligands to IL-17A and characterization of their binding site has enabled the design of novel macrocyclic ligands that are themselves potent IL-17A antagonists.

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