Development of APOBEC3B inhibitors: Recent advances and perspectives.

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2025-09-27 DOI:10.1016/j.bioorg.2025.109042

Wenjie Zhang, Yuhang Wang, Cheng Jiang

引用次数: 0

Abstract

The apolipoprotein B mRNA editing catalytic polypeptide-like 3B (A3B) is a member of the cytidine deaminase A3 family, which plays a crucial role in the viral immune process. As a cytosine deaminase, A3B is a major contributor to tumor-associated mutations. Numerous studies have shown that A3B is aberrantly expressed in a variety of tumor cells, which promotes tumor growth, migration, and drug resistance. Hence, A3B is deemed a promising candidate for potential therapeutic interventions against tumor resistance. Presently, although research on A3B inhibitors is still in its early stages, various selective inhibitors have already been reported. Notably, oligonucleotide and allosteric inhibitors have more desirable effects. In this Perspective, we encapsulate the structure, biological functions, and disease relevance of A3B. Subsequently, we summarize the literature covering various A3B inhibitors and discuss their design requirements and modes of action.

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APOBEC3B抑制剂的发展：最新进展和展望

载脂蛋白B mRNA编辑催化多肽样3B （A3B）是胞苷脱氨酶A3家族的成员，在病毒免疫过程中起着至关重要的作用。作为胞嘧啶脱氨酶，A3B是肿瘤相关突变的主要贡献者。大量研究表明，A3B在多种肿瘤细胞中异常表达，促进肿瘤生长、迁移和耐药。因此，A3B被认为是针对肿瘤耐药的潜在治疗干预的有希望的候选者。目前，虽然对A3B抑制剂的研究还处于早期阶段，但已有多种选择性抑制剂的报道。值得注意的是，寡核苷酸和变构抑制剂具有更理想的效果。在这个视角中，我们概括了A3B的结构、生物学功能和疾病相关性。随后，我们总结了涵盖各种A3B抑制剂的文献，并讨论了它们的设计要求和作用方式。

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

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.