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Gregor S Cremosnik¹, Yannick Mesrouze², Patrik Zueger¹

¹Global Discovery Chemistry, Novartis Biomedical Research, CH-4056 Basel, Switzerland.

ACS chemical biology

|April 24, 2024

概括

研究人员确定了ARID1B选择性,提供了新的癌症药物标. 这些结合ARID1B,ARID1A的类型,在ARID1A发生突变时对癌细胞生长至关重要.

科学领域:

染色体重塑复合物的复合物
癌症生物学癌症生物学
药物发现药物发现

背景情况:

ARID1A和ARID1B是SWI/SNF染色体重塑复合物的子单元.
在癌症中,ARID1A突变很常见,导致ARID1B对增殖的依赖.
由于与ARID1A.的高序列相似性,ARID1B仍然是一个非目标的对应物.

研究的目的:

为了识别ARID1B的选择性配体.
探索ARID1B作为一种潜在的药物标.
为了研究ARID1A和ARID1B在癌症中的合成致命关系.

主要方法:

利用mRNA显示来发现基连接体.
采用生物化学,生物物理和化学生物学技术进行验证.
对ARID1A.的评估结合亲和力和选择性.

主要成果:

已确定具有对ARID1B.纳米分子亲和力的基连接体.
证明了这些的ARID1B对ARID1A的高选择性.
具有两种不同的口袋的特征性结合,包括一种ARID1B专属的氨酸.

结论:

ARID1B是一种"可结合"的标,通过选择性结体进行验证.
已识别的可以作为药物发现的有价值的工具.
研究结果表明,有机会开发针对ARID1B的选择性分子,用于癌症治疗.

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