Comparative phenotypic profiling of the JAK2 inhibitors ruxolitinib, fedratinib, momelotinib, and pacritinib reveals distinct mechanistic signatures.

ABSTRACT: Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling is critical to multiple cellular processes, including survival, differentiation, and proliferation. JAK-STAT signaling dysregulation has been noted in inflammatory disorders, and aberrant JAK2 pathway activation has been implicated in myelofibrosis and polycythemia vera. Moreover, 4 therapeutic JAK2 inhibitors (ruxolitinib, fedratinib, momelotinib, and pacritinib) have either been approved or are in advanced clinical development for myelofibrosis. Although all inhibit JAK2, reports indicate that they also inhibit other kinases. Profiling based solely on in vitro potencies is insufficient to predict the observed clinical effects. To provide further translational insights into clinical outcomes, we compared

SUBMITTER: Singer JW 

PROVIDER: S-EPMC6764664 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature