Fragment-based discovery of JAK-2 inhibitors

Bioorg Med Chem Lett. 2009 Jan 1;19(1):279-82. doi: 10.1016/j.bmcl.2008.08.064. Epub 2008 Aug 22.

Abstract

Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • Drug Discovery / methods*
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / chemistry
  • Models, Molecular
  • Protein Kinase Inhibitors / chemistry*
  • Small Molecule Libraries*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Small Molecule Libraries
  • Sulfonamides
  • Janus Kinase 2