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An orally bioavailable small-molecule inhibitor of Janus kinases 1 and 2 (JAK1/2) with potential antineoplastic activity.

Mechanism of action

Momelotinib competes with JAK1 and JAK2 for ATP binding, which may result in inhibition of JAK1/2 activation, inhibition of the JAK-STAT signaling pathway, and so the induction of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor cells.


JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders; the JAK2V617F gain-of-function mutation involves a valine-to-phenylalanine modification at position 617.

JAK-STAT signaling

The JAK-STAT signaling pathway is a major mediator of cytokine activity and is often dysregulated in a variety of tumor cell types.

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