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

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-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.
Authors	A M Camoratto, J P Jani, T S Angeles, A C Maroney, C Y Sanders, C Murakata, N T Neff, J L Vaught, J T Isaacs, C A Dionne
Journal	International journal of cancer (Int J Cancer) Vol. 72 Issue 4 Pg. 673-9 (Aug 07 1997) ISSN: 0020-7136 [Print] United States
PMID	9259409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents CEP 751 Carbazoles Enzyme Inhibitors Nerve Growth Factors Proto-Oncogene Proteins Receptors, Nerve Growth Factor Tyrosine Receptor Protein-Tyrosine Kinases Receptor, trkA
Topics	3T3 Cells (metabolism, physiology) Animals Antineoplastic Agents (pharmacology) Carbazoles (pharmacology) Enzyme Inhibitors (pharmacology) Mice Nerve Growth Factors (pharmacology) PC12 Cells Phosphorylation Proto-Oncogene Proteins (antagonists & inhibitors, genetics, metabolism) Rats Receptor Protein-Tyrosine Kinases (antagonists & inhibitors, genetics, metabolism) Receptor, trkA Receptors, Nerve Growth Factor (antagonists & inhibitors, genetics, metabolism) Stimulation, Chemical Transfection Tyrosine (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!