Discovery of 1-amino-5 H-pyrido [4, 3-b] indol-4-carboxamide inhibitors of janus kinase 2 (JAK2) for the treatment of myeloproliferative disorders

…, L Xu, H Yin, J Zugay-Murphy…

Index: Lim, Jongwon; Taoka, Brandon; Otte, Ryan D.; Spencer, Kerrie; Dinsmore, Christopher J.; Altman, Michael D.; Chan, Grace; Rosenstein, Craig; Sharma, Sujata; Su, Hua-Poo; Szewczak, Alexander A.; Xu, Lin; Yin, Hong; Zugay-Murphy, Joan; Marshall, C. Gary; Young, Jonathan R. Journal of Medicinal Chemistry, 2011 , vol. 54, # 20 p. 7334 - 7349

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Citation Number: 41

Abstract

The JAK-STAT pathway mediates signaling by cytokines, which control survival, proliferation, and differentiation of a variety of cells. In recent years, a single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present with a high incidence in myeloproliferative disorders (MPDs). This mutation led to hyperactivation of JAK2, cytokine- independent signaling, and subsequent activation of downstream signaling networks. The ...