A small-molecule inhibitor of C5 complement protein

  • Nat Chem Biol. 2019 Jul;15(7):666-668. doi: 10.1038/s41589-019-0303-9.
Keith Jendza  1 ,  Mitsunori Kato  1 ,  Michael Salcius  2 ,  Honnappa Srinivas  3 ,  Andrea De Erkenez  4 ,  Anh Nguyen  4 ,  Doug McLaughlin  2 ,  Celine Be  3 ,  Christian Wiesmann  3 ,  Jason Murphy  2 ,  Philippe Bolduc  1 ,  Muneto Mogi  1 ,  Jose Duca  1 ,  Abdel Namil  1 ,  Michael Capparelli  1 ,  Veronique Darsigny  1 ,  Erik Meredith  1 ,  Ritesh Tichkule  1 ,  Luciana Ferrara  4 ,  Jessica Heyder  4 ,  Fang Liu  4 ,  Patricia A Horton  2 ,  Michael J Romanowski  2 ,  Markus Schirle  2 ,  Nello Mainolfi  1 ,  Karen Anderson  4 ,  Gregory A Michaud  5
Affiliations
  • 1. Global Discovery Chemistry, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
  • 2. Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
  • 3. Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Basel, Switzerland.
  • 4. Ophthalmology, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
  • 5. Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Cambridge, MA, USA. [email protected].
PMID: 31209353 DOI: 10.1038/s41589-019-0303-9
Abstract

The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human Complement Component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.

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