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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Effects of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, on human mast cells bearing wild-type or mutated codon 816 c-kit.

Most adults with systemic mastocytosis (SM) carry an activating mutation in the codon 816 of c-kit. We investigated the activity of the new tyrosine kinase inhibitor AMN107 on c-kit mutated mast cell lines and bone marrow samples from patients with SM and compared it to that of imatinib mesylate, a tyrosine kinase inhibitor effective in some patients with SM. In HMC-1(560) mast cells carrying wild-type codon 816 c-kit, AMN107 was very effective and as potent as imatinib in inhibiting cellular proliferation and inducing apoptosis (P<0.0823). By contrast, in HMC-1(560,816) cells bearing a c-kit mutation in codon 816, neither drug exerted a significant effect (P<0.0015). AMN107 was also as effective as imatinib in inhibiting phosphorylation of c-kit in HMC-1(560) cells. However, AMN107 had little effect on ex vivo survival of bone marrow mast cells with 816 c-kit mutation obtained from patients with SM. Based upon our results, AMN107 and imatinib are equipotent against mast cells with wild-type c-kit and those harboring the juxtamembrane D560G c-kit mutant but have no significant activity over the dose range tested against cells expressing the c-kit D816V mutant tyrosine kinase.[1]

References

  1. Effects of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, on human mast cells bearing wild-type or mutated codon 816 c-kit. Verstovsek, S., Akin, C., Manshouri, T., Quintás-Cardama, A., Huynh, L., Manley, P., Tefferi, A., Cortes, J., Giles, F.J., Kantarjian, H. Leuk. Res. (2006) [Pubmed]
 
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