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处于临床和临床前后期开发阶段的海洋来源抗癌及癌症疼痛控制药物。

Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development.

作者信息

Newman David J, Cragg Gordon M

机构信息

Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory, P.O. Box B, Frederick, MD 21702, USA.

出版信息

Mar Drugs. 2014 Jan 14;12(1):255-78. doi: 10.3390/md12010255.

Abstract

The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743), Eribulin (a synthetic derivative based on the structure of halichondrin B), and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin) as a warhead, have been approved for use in humans (Adcetris®). In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved), and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.

摘要

海洋生境产生了大量极具潜力的海洋来源药物,这些药物在体外有抑制人类肿瘤细胞生长的潜力,在许多情况下,在体内小鼠模型以及人体中也有此作用。尽管许多药物已进入癌症临床试验阶段,但迄今为止,只有阿糖胞苷、Yondelis®(ET743)、艾瑞布林(一种基于海兔毒素B结构的合成衍生物)以及多拉司他汀10衍生物单甲基澳瑞他汀E(MMAE或维泊妥珠单抗,作为弹头)已获批用于人类(Adcetris®)。在本综述中,我们展示了目前正在进行抗癌临床试验的海洋来源化合物。我们简要讨论了已获批药物,以及它们为扩展其初始获批活性而进行的试验情况(药物获批后这是常见做法),还广泛讨论了将澳瑞他汀衍生物用作弹头的情况,另外还涉及一个很少被提及的领域,即使用海洋来源药物减轻人类癌症疼痛,并作为免疫疗法的佐剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b78c/3917273/06b61e5447e3/marinedrugs-12-00255-g001.jpg

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