Antonysamy Stephen, Hirst Gavin, Park Frances, Sprengeler Paul, Stappenbeck Frank, Steensma Ruo, Wilson Mark, Wong Melissa
Medicinal Chemistry, SGX Pharmaceuticals, Inc, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2009 Jan 1;19(1):279-82. doi: 10.1016/j.bmcl.2008.08.064. Epub 2008 Aug 22.
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.
基于片段的命中化合物识别与晶体学辅助的基于结构的药物设计相结合，用于设计JAK-2的强效抑制剂。从片段1开始经过两轮迭代后，我们能够将活性提高500倍以上，得到磺酰胺13，一种78 nM的JAK-2抑制剂。
