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Updated: Jun 19, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2
Mark W Ledeboer1, Albert C Pierce, John P Duffy
1Vertex Pharmaceuticals Inc, Cambridge, MA 02139-4242, United States. mark_ledeboer@vrtx.com
Abstract:
Constitutive activation of the EPO/JAK2 signaling cascade has recently been implicated in a variety of myeloproliferative disorders including polycythemia vera, essential thrombocythemia and myelofibrosis. In an effort to uncover therapeutic potential of blocking the EPO/JAK2 signaling cascade, we sought to discover selective inhibitors that block the kinase activity of JAK2. Herein, we describe the discovery and structure based optimization of a novel series of 2-amino-pyrazolo[1,5-a]pyrimidines that exhibit potent inhibition of JAK2.
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