Antitumor activity of FCE 26644 a new growth-factor complexing molecule.
FCE 26644, or 7,7'-(carbonyl-bis[imino-N-methyl-4, 2 pyrrole carbonyl-imino(N-methyl-4,2-pyrrole)carbonyl-imino])-bis-(1,3- naphthalene)disulfonic acid, belongs to the newly synthesized class of sulfonated derivatives of distamycin A. FCE 26644 is a noncytotoxic molecule capable of inhibiting the binding of basic fibreblast growth factor (bFGF), platelet-derived growth factor (PDGF beta) and interleukin 1 (IL-7) to their receptors and to block bFGF-induced vascularization in vivo as well as neovascularization in the chorioallantoic membrane. FCE 26644 and suramin, a compound possessing the same terminal half-life (t1/2) in mice and, presumably, the same mode of action, inhibit the growth of solid murine tumors, M5076 reticulosarcoma, and MXT and S180 fibrosarcoma and are inactive against B16F10 melanoma. The activity of FCE 26644 was constantly observed at nontoxic doses, at variance with suramin. FCE 26644 was also found to maintain activity against M5076 resistant to cyclophosphamide and to be equally active against UV 2237 and UV 2237/ADR fibrosarcoma.
Sola
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F
Pharmacia-Farmitalia Carlo Erba, R&D/Business Area Oncology-Oncology Laboratory, Nerviano/Milan, Italy.
Farao
M
M
Pesenti
E
E
Marsiglio
A
A
Mongelli
N
N
Grandi
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004214:Distamycins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors; D005354:Fibrosarcoma / Q000188:drug therapy*; D006207:Half-Life; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013498:Suramin / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004214:Distamycins; C085720:FCE 26644; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D003520:Cyclophosphamide