基于磷酸二芳基的转录因子STAT4抑制剂。

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

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引用次数: 0

摘要

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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Biaryl Phosphate-Based Inhibitors of the Transcription Factor STAT4.

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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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

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.