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.
Stephen Antonysamy  1 ,  Gavin Hirst ,  Frances Park ,  Paul Sprengeler ,  Frank Stappenbeck ,  Ruo Steensma ,  Mark Wilson ,  Melissa Wong
Affiliations
  • 1. Medicinal Chemistry, SGX Pharmaceuticals, Inc, San Diego, CA 92121, USA.
PMID: 19019674 DOI: 10.1016/j.bmcl.2008.08.064
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.

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