Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol.
Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol.
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大鼠肝细胞质抗肿瘤羟甲基酰基富烯的代谢。
DOI：
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发表时间：
1999
影响因子：
3.9
通讯作者：
M. Kelner
中科院分区：
文献类型：
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作者：
T. Mcmorris;A. Elayadi;J. Yu;Y. Hu;M. Kelner
酰基黄烯是一类有效的抗肿瘤药物，从真菌倍半萜类真菌中提取。Illudin S具有抗肿瘤活性，但治疗指标较差。酰基fulvene对人肺腺癌细胞的毒性比illuudin S低100倍，但在人类异种移植物中抑制肿瘤生长，与illuudin S相反。酰基fulvene的类似物MGI 114（羟甲基酰基fulvene）显示出更大的功效，在异种移植模型中产生完全的肿瘤消退。MGI 114目前正在进行II期临床试验。MGI 114的细胞毒性与illudins一样，被认为涉及化学反应和酶还原。胞浆内nadph依赖酶（来自大鼠肝脏）的酶还原产生了一种芳香代谢物，类似于由illudin s形成的代谢物。然而，反应发生得更慢。此外，还分离到4个新的代谢物，其中2个羟基化衍生物和2个烯丙基羟基被氢化物取代的衍生物。它们都保留了母体MGI 114的活性中心。
Acylfulvenes are a potent class of antitumor agents derived from illudin S, a fungal sesquiterpene. Illudin S possesses antitumor activity but has a poor therapeutic index. Acylfulvene is 100-fold less toxic against human lung adenocarcinoma cells than illudin S, but inhibits tumor growth in human xenografts, opposite to illudin S. An analog of acylfulvene, MGI 114 (hydroxymethylacylfulvene), shows much greater efficacy, producing complete tumor regression in xenograft models. MGI 114 is currently in phase II clinical trials. Cytotoxicity of MGI 114, like that of illudin S, is believed to involve both chemical reaction and enzymatic reduction. Enzymatic reduction by a cytosolic NADPH-dependent enzyme (from rat liver) produced an aromatic metabolite similar to that formed from illudin S. However, the reaction occurred more slowly. In addition, four new metabolites were isolated, two hydroxylated derivatives and two in which the primary allylic hydroxyl was replaced by hydride. All retained the reactive centers of the parent MGI 114.
隐伞素作为抗癌药物的临床前评价。
影响因子：
11.2
作者：
Kelner,MJ;McMorris,TC;Beck,WT;Zamora,JM;Taetle,R
通讯作者：
Taetle,R