EGFRT790M和C797S基因 顺式突变 基因的研究. 在 EGFR基因中，T790M、C797S可分为顺式突变（cis）和 反式突变 （trans)，如果两个突变位于同一 DNA链上，那么T790M和C797S就是顺式突变，而在另一条 DNA上则是反式变异。

2018年7月23日 · The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition.

三代egfr抑制剂的“阿喀琉斯之踵”是egfr c797x（c797s），且随着患者长期接受一线奥希替尼治疗，egfr c797x突变的频率明显增加，因此，开发特定egfr c797x抑制剂的必要性就显得“非常重要”。

2025年1月2日 · 它是第四代 EGFR 抑制剂，在临床前模型中可以克服对奥希替尼的耐药性，并在携带 C797S 突变的 NSCLC 患者中显示出有希望的活性。 在实验模型中，BDTX-1535 抑制所有常见 EGFR 突变和 50 多种罕见突变，包括 T790M、C797S、L718X、E709X、S784F、V834L 和 A289V，然而，外显子 20 插入受到的抑制程度要小得多。 此外，EGF 受体细胞外结构域突变（例如 EGFRvII、III、IV）也可以被阻断。

C797S突变是EGFR基因第20号外显子上的一种变异，这种变异导致797位点的半胱氨酸被丝氨酸所替代，进而妨碍了奥希替尼与半胱氨酸残基的有效共价结合，引起药物耐药性。 C797S突变可以根据其与T790M突变的相对位置关系被分为三种亚型： 单纯C797S突变： 这种类型的突变通常见于接受奥希替尼一线治疗后产生耐药的患者。 T790M/C797S顺式突变：在这种情形下，T790M和C797S突变出现在同一条DNA链上。 T790M/C797S反式突变：两个突变分别位于相对的DNA …

The affinity of brigatinib to EGFR L858R/T790M/C797S was 10 times higher than that to EGFR WT, which decreased the phosphorylation of EGFR and its downstream signal pathway in a dose-dependent manner and inhibited the growth of PC9 (EGFR Del Citation 19) and PC9 (EGFR Del19/T790M) or PC9 (EGFRDel19/T790M/C797S). In addition, combining with ...

2025年3月14日 · The fourth-generation EGFR inhibitors targeting L858R/T790M/C797S mutations are in clinical trials mostly, and it is necessary to develop new inhibitors. In this study, an internal data set containing 2302 multitarget EGFR inhibitors targeting the wild type (83%) and the L858R (92%), L858R/T790M (96%), and L858R/T790M/C797S (60%) mutations was collected. We established a structure–activity ...

2024年12月19日 · This Review discusses recent advancements in the development of fourth-generation "Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs)" targeting resistance mutations, with an emphasis on the C797S …

Current research is now focused on fourth-generation EGFR-TKIs, which specifically target the EGFR harbouring the C797S mutation. This review examines the design strategies, antitumor activity both in vivo and in vitro , binding modes, pharmacokinetics, as well as the advantages and disadvantages of each inhibitor, alongside the progress of ...

2025年2月15日 · This comprehensive Review offers a detailed classification and summary of “fourth-generation EGFR-TKIs”, focusing on their structures, along with “in vitro and in vivo” studies targeting “EGFR-19Del/T790 M/C797S or EGFR-L858R/T790 M/C797S″ mutations, Structure-Activity Relationship (SAR), and protein-drug interactions. This Review ...