Grasping cryptic binding sites to neutralize drug resistance in the field of anticancer

被引：2
|
作者：
Yang, Wei-Cheng [1 ]
Gong, Dao-Hong [1 ]
Wu, Hong [1 ]
Gao, Yang-Yang [1 ]
Hao, Ge-Fei [1 ,2 ]
机构：
[1] Guizhou Univ, Ctr Res & Dev Fine Chem, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr Bioengn,Minist Educ, Guiyang 550025, Peoples R China
[2] Cent China Normal Univ, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China
来源：
DRUG DISCOVERY TODAY | 2023年 / 28卷 / 09期
基金：
中国国家自然科学基金;
关键词：
cryptic binding site; drug resistance; drug design; cancer; target drug discovery; ALLOSTERIC SITES; CANCER; INHIBITION; SELPERCATINIB; EFFICACY; CX-4945; POTENT; CELLS; COST;
D O I：
10.1016/j.drudis.2023.103705
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Drug resistance is a significant obstacle to successful cancer treatment. The utilization and development of cryptic binding sites (CBSs) in proteins involved in cancer-related drug-resistance (CRDR) could help to overcome that drug resistance. However, there is no comprehensive review of the successful use of CBSs in addressing CRDR proteins. Here, we have systematically summarized and analyzed the opportunities and challenges of using CBSs in addressing CRDR proteins and revealed the key role that CBSs have in targeting CRDR proteins. First, we have identified the CRDR targets and the corresponding CBSs. Second, we discuss the mechanisms by which CBSs can overcome CRDR proteins. Finally, we have provided examples of successful CBS applications in addressing CRDR proteins. We hope that this approach will provide guidance to biologists and chemists in effectively utilizing CBSs for the development of new drugs to alleviate CRDR.
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收藏
页数：9
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