Targeting Gatekeeper Mutations for Kinase Drug Discovery,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 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.)

Targeting Gatekeeper Mutations for Kinase Drug Discovery
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-11-17 , DOI: 10.1021/acs.jmedchem.2c01361
Yang Zhou ₁ , Shuang Xiang ₁ , Fang Yang ₁ , Xiaoyun Lu ₁

Affiliation

Clinically acquired resistance is a major challenge in cancer therapies with small-molecule kinase inhibitors (SMKIs). Gatekeeper mutations in the ATP-binding pocket of kinases are the most common mutations leading to acquired resistance. To date, seven new-generation kinase inhibitors targeting gatekeeper mutations have been approved by the FDA; however, the clinical need is still unmet. Here, we systematically summarize the types of gatekeeper mutations across the kinase family, the structural basis for acquired resistance, and newly developed SMKIs targeting gatekeeper mutations as well as highlight the opportunities and challenges of kinase drug discovery for targeting gatekeeper mutations.

中文翻译：

针对激酶药物发现的看门人突变

临床获得性耐药是使用小分子激酶抑制剂 (SMKI) 进行癌症治疗的主要挑战。激酶 ATP 结合口袋中的看门人突变是导致获得性耐药性的最常见突变。迄今为止，已有七种针对守门人突变的新一代激酶抑制剂获得了 FDA 的批准；然而，临床需求仍未得到满足。在这里，我们系统地总结了整个激酶家族的看门人突变类型、获得性耐药的结构基础和新开发的针对看门人突变的 SMKI，并强调了针对看门人突变的激酶药物发现的机遇和挑战。

更新日期：2022-11-17

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