Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products.
Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products.
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DOI：
10.1039/c9np00053d
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发表时间：
2020-05-01
影响因子：
11.9
通讯作者：
Du L
中科院分区：
文献类型：
--
作者：
Risinger AL;Du L
我们回顾了靶向细胞骨架成分的天然产物的最新进展，包括微管、肌动蛋白、中间丝和septin，并强调了它们在治疗人类疾病中的已证实和潜在应用。从植物、微生物和海洋生物中鉴定出的微管靶向药物的抗癌功效已得到充分证明。我们重点介绍了目前正在临床评估中用于治疗耐药癌症的新型微管靶向药物，以及越来越多的证据表明这些药物的抗癌功效不仅仅是由于它们的抗有丝分裂作用。事实上，微管靶向药物对间期微管的作用正在导致它们在癌症和神经系统疾病中更机械地指导使用的潜力。这些药物作为更有针对性的药物的讨论也促使我们对靶向细胞骨架其他成分的天然产物的思考进行重新评估。例如，肌动蛋白活性天然产物在很大程度上被认为是化学探针和非选择性毒素。然而，利用这些探针的研究已经揭示了肌动蛋白生物学的一些方面，这些方面可以更具体地靶向治疗癌症、神经系统疾病和传染病。靶向中间纤维和septin的化合物尚未得到充分研究，但它们的持续发现和机制评估对许多治疗适应症具有重要意义。
We review recent progress on natural products that target cytoskeletal components, including microtubules, actin, intermediate filaments, and septins and highlight their demonstrated and potential utility in the treatment of human disease. The anticancer efficacy of microtubule targeted agents identified from plants, microbes, and marine organisms is well documented. We highlight new microtubule targeted agents currently in clinical evaluations for the treatment of drug resistant cancers and the accumulating evidence that the anticancer efficacy of these agents is not solely due to their antimitotic effects. Indeed, the effects of microtubule targeted agents on interphase microtubules are leading to their potential for more mechanistically guided use in cancers as well as neurological disease. The discussion of these agents as more targeted drugs also prompts a reevaluation of our thinking about natural products that target other components of the cytoskeleton. For instance, actin active natural products are largely considered chemical probes and non-selective toxins. However, studies utilizing these probes have uncovered aspects of actin biology that can be more specifically targeted to potentially treat cancer, neurological disorders, and infectious disease. Compounds that target intermediate filaments and septins are understudied, but their continued discovery and mechanistic evaluations have implications for numerous therapeutic indications.
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影响因子：
3.4
作者：
Das, Viswanath;Miller, John H.
通讯作者：
Miller, John H.
DOI：
10.1073/pnas.1716009114
发表时间：
2017-11-14
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Spiliotis, Elias T.
影响因子：
5
作者：
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通讯作者：
Soon-Shiong, Patrick
影响因子：
5.8
作者：
Andersen, Raymond J.
通讯作者：
Andersen, Raymond J.