CEP-751 inhibits trk receptor tyrosine kinase activity in vitro and exhibits anti-tumor activity

Anna Marie Camoratto, Jitesh P. Jani, Thelma S. Angeles, Anna C. Maroney, Christa Y. Sanders, Chikara Murakata, Nicola T. Neff, Jeffry L. Vaught, John T. Isaacs, Craig A. Dionne

Research output: Contribution to journalArticlepeer-review

Abstract

The present report describes the in vitro and in vivo profile of CEP- 751, a novel receptor tyrosine kinase inhibitor. CEP-751 at 100 nM inhibits the receptor tyrosine kinase activity of the neurotrophin receptors trkA, trkB and trkC. CEP-751 has no effect on activity of receptors for EGF, IGF- 1, insulin or on erbB2; inhibition of receptors for PDGF and bFGF was observed but occurred with lesser potency than inhibition of trk. CEP-751 exhibited anti-tumor efficacy against tumors derived from NIH3T3 cells transfected with trkA. Inhibition of trk phosphorylation could also be measured in these tumors, suggesting that anti-tumor efficacy of CEP-751 is related to inhibition of trk receptor tyrosine kinase activity. CEP-751 was found to be without effect when administered to nude mice bearing SK-OV-3 tumors, which overexpress erbB2 receptors, providing further evidence that inhibition of tumor growth may be related to inhibition of trk receptor tyrosine kinase activity. Our data indicate that CEP-751 is a potent trk inhibitor which possesses anti-tumor activity.

Original languageEnglish (US)
Pages (from-to)673-679
Number of pages7
JournalInternational Journal of Cancer
Volume72
Issue number4
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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