NCIt definition : An orally bioavailable small molecule inhibitor of wild-type (WT) Janus kinases 1
and 2 (JAK1/2), the JAK2 mutant form JAK2V617F, and activin A receptor type 1 (ACVR1;
activin receptor like kinase 2; ALK2), with antineoplastic activity. Upon oral administration,
momelotinib competes with JAK1/2 for ATP binding, which results in inhibition of JAK1/2
activation, inhibition of the JAK-STAT signaling pathway, and leads to the induction
of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor
cells. In addition, the inhibition of ALK2 prevents liver hepcidin formation, increases
iron availability and increases red blood cell (RBC) production. 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. The JAK-STAT signaling pathway is a major mediator of cytokine activity and is
often dysregulated in a variety of tumor cell types.;
UNII : 6O01GMS00P;
InChIKey : ZVHNDZWQTBEVRY-UHFFFAOYSA-N;
CAS number : 1056634-68-4;
Molecule name : CYT-387; GS-0387; CYT 387; GS 0387;