相关实验视频

Updated: Jul 5, 2025

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

基于结构的可逆KRAS G13D抑制剂的设计和评估

Christian Nilewski¹, Sharada Labadie¹, Binqing Wei¹

¹Genentech Inc., 1 DNA Way, South San Francisco, California 94080, United States.

ACS medicinal chemistry letters

|January 17, 2024

概括

研究人员开发了新的可逆抑制剂,针对KRAS G13D突变,这是一个具有挑战性的癌症标. 这些抑制剂通过与D13残留物形成盐桥来实现高强度和选择性.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

瘤性KRAS突变是各种癌症的成熟驱动因素.
向KRAS G12C已经通过共价抑制显示出临床成功.
选择性抑制其他KRAS突变,如KRAS G13D,仍然是一个重大挑战.

研究的目的:

为KRAS G13D.设计和评估新型,强效和选择性抑制剂.
为了克服与准KRAS G13D突变相关的挑战.

主要方法:

基于结构的药物设计利用与D13残留物的相互作用.
对KRAS G13D.的GDP-bound状态的抑制剂结合 afinity 的评估.
生物化学测试以评估对野生类型 (WT) KRAS的选择性.

主要成果:

开发具有亚纳米分子结合亲和力的强效可逆抑制剂.
在KRAS G13D与WT KRAS之间实现了高的生物化学选择性.
抑制剂的设计利用盐桥相互作用与D13残留物.

结论:

成功设计了KRAS G13D选择性可逆抑制剂.
开发的抑制剂代表了针对KRAS G13D突变癌症的有希望的策略.
利用特定的残留物相互作用,如D13盐桥,对选择性KRAS抑制是有效的.

更多相关视频

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

相关概念视频

Structure-Activity Relationships and Drug Design

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...