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

Int J Cancer. 1997 Aug 7;72(4):673-9. doi: 10.1002/(sici)1097-0215(19970807)72:4<673::aid-ijc20>3.0.co;2-b.


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-I, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / metabolism
  • 3T3 Cells / physiology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Mice
  • Nerve Growth Factors / pharmacology
  • PC12 Cells
  • Phosphorylation
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, trkA
  • Receptors, Nerve Growth Factor / antagonists & inhibitors*
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Stimulation, Chemical
  • Transfection
  • Tyrosine / metabolism


  • Antineoplastic Agents
  • CEP 751
  • Carbazoles
  • Enzyme Inhibitors
  • Nerve Growth Factors
  • Proto-Oncogene Proteins
  • Receptors, Nerve Growth Factor
  • Tyrosine
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA