7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors
7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors
复制标题
DOI：
10.1016/j.bmc.2013.12.031
复制
发表时间：
2014-02-01
影响因子：
3.5
通讯作者：
Dallavalle, Sabrina
中科院分区：
文献类型：
--
作者：
Cincinelli, Raffaella;Musso, Loana;Dallavalle, Sabrina
7-氮杂环己烷-1-甲酰胺类化合物是一类新型的PARP-1抑制剂。这些化合物表现出不同的靶向抑制模式，部分地与以同源重组缺陷为特征的细胞系的抗增殖活性平行。一种选定的化合物(1L；ST7710AA1)在体外显示出显著的靶向抑制和基本上绕过Pgp介导的多药耐药的能力。在对裸鼠体内MX1人乳腺癌生长的抗肿瘤活性研究中，当使用低于参考化合物的剂量时，该化合物在抑制肿瘤体积方面表现出与奥拉帕利相似的效果。治疗耐受性良好，因为在接受治疗的动物中没有观察到死亡或显著的体重减轻。(C)2013爱思唯尔有限公司。保留所有权利。
7-Azaindole-1-carboxamides were designed as a new class of PARP-1 inhibitors. The compounds displayed a variable pattern of target inhibition profile that, in part, paralleled the antiproliferative activity in cell lines characterized by homologous recombination defects. A selected compound (1l; ST7710AA1) showed significant in vitro target inhibition and capability to substantially bypass the multidrug resistance mediated by Pgp. In antitumor activity studies against the MX1 human breast carcinoma growth in nude mice, the compound exhibited an effect similar to that of Olaparib in terms of tumor volume inhibition when used at a lower dose than the reference compound. Treatment was well tolerated, as no deaths or significant weight losses were observed among the treated animals. (C) 2013 Elsevier Ltd. All rights reserved.