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聚腺苷二磷酸核糖聚合酶抑制剂在非肿瘤性疾病治疗中的再利用机会。

Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases.

机构信息

Center for Science, Health and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

EA4475 - Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

出版信息

Br J Pharmacol. 2018 Jan;175(2):192-222. doi: 10.1111/bph.13748. Epub 2017 Mar 26.

Abstract

UNLABELLED

The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors.

LINKED ARTICLES

This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

摘要

未加标签

聚 ADP 核糖聚合酶(PARP)抑制剂奥拉帕尼(Lynparza)最近在临床上的应用为非肿瘤适应症的潜在治疗用途开辟了道路。考虑到(a)PARP 抑制剂在非肿瘤疾病中的临床前疗效数据,以及(b)用抑制在调节 DNA 修复中具有生理作用的酶的化合物治疗患者的风险-效益比,我们选择了以下适应症:(a)疾病的严重程度高,(b)可用的治疗选择有限,以及(c)PARP 抑制剂的治疗时间可能很短,为治疗用途的重新定位提供一线选择。这些适应症如下:急性缺血性中风;创伤性脑损伤;感染性休克;急性胰腺炎;严重哮喘和严重急性肺损伤。此外,还应考虑慢性、破坏性疾病,替代治疗选择无法阻止疾病发展(如帕金森病、进行性多发性硬化症或严重纤维化疾病)。我们提出了 PARP 抑制剂重新定位的临床前和临床行动计划。

相关文章

本文是关于发明新药而非从头开始:药物再利用的力量的专题部分的一部分。要查看该部分中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

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