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新型生长因子复合分子FCE 26644的抗肿瘤活性

Antitumor activity of FCE 26644 a new growth-factor complexing molecule.

作者信息

Sola F, Farao M, Pesenti E, Marsiglio A, Mongelli N, Grandi M

机构信息

Pharmacia-Farmitalia Carlo Erba, R&D/Business Area Oncology-Oncology Laboratory, Nerviano/Milan, Italy.

出版信息

Cancer Chemother Pharmacol. 1995;36(3):217-22. doi: 10.1007/BF00685849.

Abstract

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.

摘要

FCE 26644,即7,7'-(羰基-双[亚氨基-N-甲基-4,2-吡咯羰基-亚氨基(N-甲基-4,2-吡咯)羰基-亚氨基])-双-(1,3-萘)二磺酸,属于新合成的放线菌素A磺化衍生物类。FCE 26644是一种无细胞毒性的分子,能够抑制碱性成纤维细胞生长因子(bFGF)、血小板衍生生长因子(PDGFβ)和白细胞介素1(IL-7)与其受体的结合,并在体内阻断bFGF诱导的血管生成以及绒毛尿囊膜中的新生血管形成。FCE 2664维和苏拉明(一种在小鼠体内具有相同终末半衰期(t1/2)且推测作用方式相同的化合物)可抑制实体小鼠肿瘤、M5076网状肉瘤、MXT和S180纤维肉瘤的生长,而对B16F10黑色素瘤无活性。与苏拉明不同,在无毒剂量下可持续观察到FCE 26644的活性。还发现FCE 26644对环磷酰胺耐药的M5076保持活性,并且对UV 2237和UV 2237/ADR纤维肉瘤同样有活性。

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