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

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 134 KB
• Volume: 72
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970807)72:4<673::aid-ijc20>3.0.co;2-b

✦ Synopsis

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.