Biaryl Phosphate-Based Inhibitors of the Transcription Factor STAT4.

IF 3.4 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-09-09 DOI:10.1002/cmdc.202500672

Nadiya Brovchenko, Anne Maria Oelsch, Christoph Protzel, Thorsten Berg

引用次数: 0

Abstract

The transcription factor signal transducer and activator of transcription (STAT)4 is a potential target for autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and diabetes mellitus. p-Biphenyl phosphate is reported as an inhibitor of the STAT4 Src homology 2 domain, and it is developed to the phosphonate-based inhibitor Stafori-1. Herein, structure-activity relationships of p-biaryl phosphates against STAT4 and their selectivity profiles against other STAT proteins are reported. The most potent biaryl phosphate-based inhibitor originating from this article, Stafori-2, contains the same aryl moieties as the phosphonate Stafori-1. However, Stafori-2 is more potent than Stafori-1 in fluorescence polarization assays and by isothermal titration calorimetry.

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基于磷酸二芳基的转录因子STAT4抑制剂。

转录因子信号换能器和转录激活因子（STAT）4是自身免疫性疾病的潜在靶点，如炎症性肠病、多发性硬化症、类风湿性关节炎和糖尿病。磷酸对联苯酯（p-Biphenyl phosphate）被报道为stat4src同源2结构域的抑制剂，并发展为基于磷酸盐的抑制剂Stafori-1。本文报道了磷酸二芳基对STAT4的结构-活性关系及其对其他STAT蛋白的选择性。本文中最有效的磷酸二芳基抑制剂Stafori-2含有与磷酸二芳基抑制剂Stafori-1相同的芳基部分。然而，在荧光偏振分析和等温滴定量热法中，Stafori-2比Stafori-1更有效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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