Review on target domains and natural compound-based inhibitors of fatty acid synthase for anticancer drug discovery,Chemical Biology & Drug Design

当前位置： X-MOL 学术 › Chem. Bio. Drug Des. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Review on target domains and natural compound-based inhibitors of fatty acid synthase for anticancer drug discovery
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2021-08-30 , DOI: 10.1111/cbdd.13942
Lakshmi Soukya Sai Pulla ₁ , Sajeli Begum Ahil ₁

Affiliation

Cancer cells require a higher amount of energy in the form of fatty acids for their uncontrolled proliferation and growth. Fatty acid synthase (FASN) plays a crucial role in the synthesis of palmitate, which is involved in most of the critical malignant pathways. Hence, by targeting FASN, tumour growth can be controlled. By designing and developing FASN inhibitors with catalytic domain specificity, safe and potential anticancer drugs can be achieved. The article draws light towards the catalytic domains of FASN, their active site residues and interaction of some of the reported natural FASN inhibitors (resveratrol, lavandulyl flavonoids, catechins, stilbene derivatives, etc). The rationality (structure–activity relationship) behind the variation in the activity of the reported natural FASN inhibitors (butyrolactones, polyphenolics, galloyl esters and thiolactomycins) has also been covered. Selective, safe and potentially active FASN inhibitors could be developed by: (i) having proper understanding of the function of all catalytic domains of FASN (ii) studying the upstream and downstream FASN regulators (iii) identifying cancer-specific FASN biomarkers (that are non-essential/absent in the normal healthy cells) (iv) exploring the complete protein structure of FASN, e-screening of the compounds prior to synthesis and study their ADME properties (v) predicting the selectivity based on their strong affinity at the catalytic site of FASN.

中文翻译：

用于抗癌药物发现的脂肪酸合酶靶域和天然化合物抑制剂综述

癌细胞需要更多以脂肪酸形式存在的能量来实现不受控制的增殖和生长。脂肪酸合酶 (FASN) 在棕榈酸的合成中起着至关重要的作用，棕榈酸参与了大多数关键的恶性途径。因此，通过靶向 FASN，可以控制肿瘤的生长。通过设计和开发具有催化域特异性的 FASN 抑制剂，可以获得安全且具有潜力的抗癌药物。这篇文章重点介绍了 FASN 的催化结构域、它们的活性位点残基以及一些已报道的天然 FASN 抑制剂（白藜芦醇、薰衣草基类黄酮、儿茶素、芪衍生物等）的相互作用。报道的天然 FASN 抑制剂（丁内酯、多酚、没食子酸酯和硫代乳霉素）也包括在内。选择性、安全和潜在活性的 FASN 抑制剂可以通过以下方式开发：（i）正确理解 FASN 的所有催化结构域的功能（ii）研究上游和下游 FASN 调节剂（iii）识别癌症特异性 FASN 生物标志物（即在正常健康细胞中非必需/不存在）（iv）探索 FASN 的完整蛋白质结构，在合成前对化合物进行电子筛选并研究其 ADME 特性（v）基于它们对催化的强亲和力预测选择性FASN 网站。

更新日期：2021-10-29

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11