PDF(Pubmed)
Abstract：
The identification of new targets to address unmet medical needs, better in a personalized way, is an urgent necessity. The introduction of PARP1 inhibitors into therapy, almost ten years ago, has represented a step forward this need being an innovate cancer treatment through a precision medicine approach. The PARP family consists of 17 members of which PARP1 that works by poly-ADP ribosylating the substrate is the sole enzyme so far exploited as therapeutic target. Most of the other members are mono-ADP-ribosylating (mono-ARTs) enzymes, and recent studies have deciphered their pathophysiological roles which appear to be very extensive with various potential therapeutic applications. In parallel, a handful of mono-ARTs inhibitors emerged that have been collected in a perspective on 2022. After that, additional very interesting compounds were identified highlighting the hot-topic nature of this research field and prompting an update. From the present review, where we have reported only mono-ARTs inhibitors endowed with the appropriate profile of pharmacological tools or drug candidate, four privileged scaffolds clearly stood out that constitute the basis for further drug discovery campaigns.
摘要：
确定新的目标，以解决未满足的医疗需求，以个性化的方式更好，是迫切需要。将PARP1抑制剂引入治疗中，差不多十年前,代表了通过精准医学方法创新癌症治疗的需要向前迈出了一步。PARP家族由17个成员组成,其中通过聚ADP核糖基化底物起作用的PARP1是迄今为止用作治疗靶标的唯一酶。大多数其他成员是单ADP核糖基化（单ARTs）酶，最近的研究已经破译了它们的病理生理作用，这些作用似乎非常广泛，具有各种潜在的治疗应用。并行,出现了一些单-ARTs抑制剂，这些抑制剂已于2022年收集。之后,确定了其他非常有趣的化合物，突出了该研究领域的热门话题性质，并促使更新。从目前的审查来看，我们仅报道了具有适当药理学工具或候选药物的单-ARTs抑制剂，四个特权脚手架显然脱颖而出，构成了进一步药物发现运动的基础。
