Peptide-linked 1,3-dialkyl-3-acyltriazenes: gastrin receptor directed antineoplastic alkylating agents.
Peptide-linked 1,3-dialkyl-3-acyltriazenes: gastrin receptor directed antineoplastic alkylating agents.
复制标题
肽连接的 1,3-二烷基-3-酰基三氮烯：胃泌素受体定向抗肿瘤烷化剂。
DOI：
10.1021/jm00048a016
复制
发表时间：
1994
影响因子：
7.3
通讯作者：
Michejda,CJ
中科院分区：
文献类型：
--
作者：
Schmidt,BF;Hernandez,L;Rouzer,C;Czerwinski,G;Chmurny,G;Michejda,CJ
The gastrin receptor is expressed in various human cancers, such as the adenocarcinoma of the colon. Thepeptide hormone gastrin and the C-terminal peptides derived from it act as growth factors for these cancers. The hypothesis for the present work was to use the gastrin receptor as a target for appropriately constructed cytotoxic agents. We developed methods to link tetragastrin and pentagastrin by their N-termini to cytotoxicl-(2-chloroethyl)-3-benzyl-3-succinoyltriazene. These compounds, CBS-4 and CBS-5, respectively, whose complete structures were determined by multinuclear NMR and mass spectrometry, competed effectively with gastrin in an assay using either guinea pig stomach fundus or the rat acinar tumor cell line AR42J as the source of the receptor. CBS-5 was cytotoxic to AR42J cells but was not toxic to A549 human lung cancer cells, which do not express the receptor.
