相关实验视频

Updated: Sep 11, 2025

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

选择性YTHDF1抑制剂的识别针对m6乳腺癌的识别域

Yongya Wu¹, Guotai Feng¹, Wen Shuai¹

¹State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Children's Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, 610041, China.

Angewandte Chemie (International ed. in English)

|August 19, 2025

概括

研究人员开发了SKLB-Y13,这是第一个针对YTHDF1的选择性抑制剂,YTHDF1是一种与乳腺癌相关的蛋白质. 这种小分子破坏癌细胞生长,并通过抑制YTHDF1来促进细胞亡.

科学领域:

生物化学生物化学
分子生物学分子生物学
在瘤学瘤学.

背景情况:

含有YTH域的家族蛋白1 (YTHDF1) 是一个关键的N6-甲基氨酸 (m6A) 读取器,参与蛋白质合成.
异常的YTHDF1表达与乳腺癌 (BC) 的进展有关.
由于YTH域同质性,现有的YTHDF1抑制剂缺乏选择性和有效性.

研究的目的:

开发第一个专门针对YTHDF1.1的小分子抑制剂.
研究选择性YTHDF1抑制在乳腺癌中的治疗潜力.

主要方法:

结构优化一个4,5,6,7-四二[2,3-c]里丁支架,以创建SKLB-Y13.
局部定向突变发生,以确认与YTHDF1特异性残留物 (Tyr397和Trp470) 的相互作用.
细胞和体内研究,化学蛋白质组学和药理动力学分析.

主要成果:

SKLB-Y13选择性地针对YTHDF1的m6A结合口袋,其IC50为0.76μM.
SKLB-Y13对YTHDF1比其他YTH家族蛋白质具有更高的选择性.
SKLB-Y13破坏了YTHDF1-PRPF6mRNA的相互作用,抑制了BC的增殖,并促进了亡.

结论:

SKLB-Y13是第一个选择性YTHDF1抑制剂,为m6A依赖性瘤发生研究提供了一种新的化学探针.
这种抑制剂显示出作为针对YTHDF1-过度表达乳腺癌的精密疗法的起点的希望.

关键词:

防止核武器的扩散.乳腺癌是什么? 乳腺癌是什么?药物发现药物发现选择性抑制剂的选择性抑制剂在 YTHDF1 的位置上.

更多相关视频

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...