Efforts to Develop KRAS Inhibitors

被引：29

作者：

Holderfield, Matthew ^{[1
]}

机构：

[1] NCI, Ras Initiat, Canc Res Technol Program, Frederick Natl Lab Canc Res,Leidos Biomed Res, Frederick, MD 21702 USA

来源：

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE | 2018年 / 8卷 / 07期

基金：

美国国家卫生研究院;

关键词：

K-RAS ONCOGENE; STRUCTURAL BASIS; LUNG-CARCINOMA; PDE-DELTA; EFFECTOR INTERACTIONS; PROTEIN TRANSFERASE; TRANSFORMING GENES; DRUG-SENSITIVITY; CANCER-CELLS; B-RAF;

D O I：

10.1101/cshperspect.a031864

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The high prevalence of KRAS mutations in human cancers and the lack of effective treatments for patients ranks KRAS among the most highly sought-after targets for preclinical oncologists. Pharmaceutical companies and academic laboratories have tried for decades to identify small molecule inhibitors of oncogenic KRAS proteins, but little progress has been made and many have labeled KRAS undruggable. However, recent progress in in silico screening, fragment-based drug design, disulfide tethered screening, and some emerging themes in RAS biology have caused the field to reconsider previously held notions about targeting KRAS. This review will cover some of the historical efforts to identify RAS inhibitors, and some of the most promising efforts currently being pursued.

引用

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