Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFR-α-expressing cells

Srdan Verstovsek, Francis J. Giles, Alfonso Quintás-Cardama, Taghi Manshouri, Ly Huynh, Paul Manley, Jorge Cortes, Ayalew Tefferi, Hagop Kantarjian

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by tissue involvement and organ dysfunction due to abnormal eosinophil proliferation. In a subset of patients, this is caused by the FIP1L1-PDGFR-α fusion tyrosine kinase. Cumulative evidence indicates that the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (Gleevec) is active for the treatment of patients with HES, particularly those expressing the FIP1L1-PDGFR-α oncoprotein. The novel tyrosine kinase inhibitor AMN107 was initially developed as a potent Bcr-Abl inhibitor based on the molecular structure of imatinib. We tested the in vitro efficacy of imatinib and AMN107 in the EOL-1 cell line and in cells from a patient with HES harboring the FIP1L1-PDGFR-α fusion kinase. AMN107 was as potent as imatinib in inducing apoptosis and inhibiting proliferation of EOL-1 cells, with IC50 values of 0.54 and 0.20 nM, respectively. In addition, both drugs inhibited the phosphorylation of PDGFR-α tyrosine kinase with equivalent efficacy. We conclude that AMN107 and imatinib are active and equipotent against cells expressing the FIP1L1-PDGFR-α fusion gene.

Original languageEnglish (US)
Pages (from-to)1499-1505
Number of pages7
JournalLeukemia Research
Volume30
Issue number12
DOIs
StatePublished - Dec 1 2006

Keywords

  • AMN107
  • Hypereosinophilic syndrome
  • Imatinib
  • PDGFR-α

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFR-α-expressing cells'. Together they form a unique fingerprint.

  • Cite this

    Verstovsek, S., Giles, F. J., Quintás-Cardama, A., Manshouri, T., Huynh, L., Manley, P., Cortes, J., Tefferi, A., & Kantarjian, H. (2006). Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFR-α-expressing cells. Leukemia Research, 30(12), 1499-1505. https://doi.org/10.1016/j.leukres.2006.03.012