FOUR Small Molecule Inhibition of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4)

N.E. Genung, K.M. Guckian

Biogen, Cambridge, MA, United States

Contents

  • 1. Introduction 118
  • 1.1 IRAK4 and TLR/IL-1R Signalling Pathways 118
  • 1.2 IRAK4 Structure and Function 120
  • 1.3 Therapeutic Potential of IRAK4 Inhibition 121
  • 2. Small Molecule IRAK4 Inhibitor Discovery 125
  • 2.1 Ares Trading S.A. 125
  • 2.2 Astellas Pharma Inc. 125
  • 2.3 Aurigene Discovery Technologies Limited 127
  • 2.4 Bayer Pharma 128
  • 2.5 Biogen 130
  • 2.6 Bristol-Meyers Squibb 132
  • 2.7 Hoffmann-La Roche 135
  • 2.8 Ligand Pharmaceuticals 135
  • 2.9 Merck Serono/KGaA 137
  • 2.10 Merck Sharp and Dohme Corp. 139
  • 2.11 Nimbus Therapeutics 147
  • 2.12 Pfizer, Inc. 151
  • 2.13 Tularik/Amgen 153
  • 2.14 Takeda Pharmaceutical Company Limited 154
  • 3. Summary of Clinical Status 155
  • 4. Conclusion 156

References 156

Keywords: IRAK4, Small molecule, Serine-threonine kinase, TLR signaling, Structure- based drug design, Autoimmune, Inflammation, Neurodegenerative

© 2017 Elsevier B.V. All rights reserved.

Progress in Medicinal Chemistry, Volume 56 ISSN 0079-6468

http://dx.doi.org/10.1016/bs.pmch.2016.11.004

 
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