Discovery of potent ureido tetrahydrocarbazole derivatives for cancer treatments through targeting tumor-associated macrophages.
Discovery of potent ureido tetrahydrocarbazole derivatives for cancer treatments through targeting tumor-associated macrophages.
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发现有效的脲基四氢咔唑衍生物，通过靶向肿瘤相关巨噬细胞来治疗癌症。
DOI：
10.1016/j.ejmech.2019.111741
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发表时间：
2019-12
影响因子：
6.7
通讯作者：
Chen Yihua
中科院分区：
文献类型：
--
作者：
Pei Haixiang;Qin Juliang;Wang Fengmian;Tan Binghe;Zhao Zeda;Peng Yangrui;Yu Fangfei;Li Ennian;Liu Mingyao;Zhang Rong;Liu Bo;Du Bing;Chen Yihua
肿瘤相关巨噬细胞（TAM）是肿瘤微环境（TME）的重要组成部分之一。TAM的极化特性驱使它们在癌症中以M1（抗肿瘤）和M2（促肿瘤）表型之间的状态渗透和活化。利用小分子药物靶向治疗肿瘤，使其具有抗肿瘤表型，是近年来肿瘤治疗的新策略。为了寻找靶向TAMs的新型化合物，设计、合成了一系列脲基四氢咔唑衍生物，并对其进行了体外和体内评价。其中化合物23 a在体内和体外均能剂量依赖性地将TAM从M2恢复到M1。更重要的是，体内实验还显示化合物23 a能够显著抑制LLC小鼠模型的肿瘤生长。此外，化合物23 a与抗PD-1抗体的协同作用比单独使用两者具有更上级的体内抗肿瘤作用。
Tumor-associated macrophages (TAMs) are one of the prominent components of the tumor microenvironment (TME). The polarization peculiarity of TAMs drives them to infiltrate and active with states between M1 (anti-tumor) and M2 (pro-tumor) phenotypes in cancers. Exploiting small molecular drugs through targeting TAMs to repolarize them into an antitumor phenotype is considered as a novel strategy for cancer treatments in recent years. For discovering novel compounds that target TAMs, a series of ureido tetrahydrocarbazole derivatives were designed, synthesized and evaluated bothin vitroandin vivo. Among them, compound23awas found to dose-dependently repolarize TAMs from M2 to M1 bothin vitroandin vivo. And more importantly, thein vivoexperiments also revealed that compound23awas capable of remarkably inhibiting tumor growth of the LLC mouse model. Moreover, the synergy of compound23awith anti-PD-1 antibody had more superior antineoplastic effects than the exclusive use of eitherin vivo.
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DOI：
10.1002/path.1918
发表时间：
2006-03
期刊：
The Journal of Pathology
影响因子：
--
作者：
H. Zijlmans;G. Fleuren;H. Baelde;P. Eilers;G. Kenter;A. Gorter
通讯作者：
H. Zijlmans;G. Fleuren;H. Baelde;P. Eilers;G. Kenter;A. Gorter
影响因子：
28.2
作者：
Kaneda MM;Cappello P;Nguyen AV;Ralainirina N;Hardamon CR;Foubert P;Schmid MC;Sun P;Mose E;Bouvet M;Lowy AM;Valasek MA;Sasik R;Novelli F;Hirsch E;Varner JA
通讯作者：
Varner JA
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
8.8
作者：
Jenkins RW;Barbie DA;Flaherty KT
通讯作者：
Flaherty KT
影响因子：
8.8
作者：
Kratochvill F;Neale G;Haverkamp JM;Van de Velde LA;Smith AM;Kawauchi D;McEvoy J;Roussel MF;Dyer MA;Qualls JE;Murray PJ
通讯作者：
Murray PJ