ai开发的肠道限制性PHD抑制剂的肠黏膜屏障修复和免疫调节

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2024-12-11 DOI:10.1038/s41587-024-02503-w

Yanyun Fu, Xiao Ding, Man Zhang, Chunlei Feng, Ziqi Yan, Feng Wang, Jianyu Xu, Xiaoxia Lin, Xiaoyu Ding, Ling Wang, Yaya Fan, Taotao Li, Yushu Yin, Xing Liang, Chenxi Xu, Shan Chen, Fadi E. Pulous, David Gennert, Frank W. Pun, Petrina Kamya, Feng Ren, Alex Aliper, Alex Zhavoronkov

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引用次数: 0

摘要

缺氧诱导因子脯氨酸羟化酶（PHD）抑制剂已被批准用于治疗肾性贫血，但由于缺乏疗效，在炎症性肠病的临床试验中失败。在这里，我们使用多模型多模式生成人工智能平台设计了一种口服肠道限制性选择性PHD1和PHD2抑制剂，在临床前研究中表现出良好的安全性和药代动力学特征。ISM012-042在多种实验性结肠炎模型中恢复肠道屏障功能，减轻肠道炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor

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Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

期刊介绍： Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research. The journal serves researchers by providing peer-reviewed research papers in the field of biotechnology. It also serves the business community by delivering news about research developments. This approach ensures that both the scientific and business communities are well-informed and able to stay up-to-date on the latest advancements and opportunities in the field. Some key areas of interest in which the journal actively seeks research papers include molecular engineering of nucleic acids and proteins, molecular therapy, large-scale biology, computational biology, regenerative medicine, imaging technology, analytical biotechnology, applied immunology, food and agricultural biotechnology, and environmental biotechnology. In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.