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  • An orally bioavailable inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. Upon oral administration, WP1066 specifically binds to both JAK2 and its mutated form, JAK2 V617F, and inhibits their phosphorylation and activation. In addition, this agent degrades JAK2 protein. This results in the inhibition of the JAK- signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase (PI3K)/AKT signaling pathways, resulting in the induction of apoptosis in tumor cells overexpressing JAK2. JAK2, a tyrosine kinase, is overexpressed in a variety of tumor cells and is correlated with increased tumor cell proliferation and survival. The mutated form JAK2 V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival.
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