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Development of APOBEC3B inhibitors: Recent advances and perspectives
Wenjie Zhang1, Yuhang Wang1, Cheng Jiang1
1School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
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.
Insights
Apolipoprotein B mRNA editing catalytic polypeptide-like 3B (A3B) is a key player in viral immunity and tumor mutations. Inhibitors targeting A3B show promise for overcoming tumor drug resistance.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Apolipoprotein B mRNA editing catalytic polypeptide-like 3B (A3B) is a cytidine deaminase involved in viral immunity.
- A3B contributes to tumor-associated mutations and is aberrantly expressed in various cancers.
- Its role in promoting tumor growth, migration, and drug resistance makes it a therapeutic target.
Purpose of the Study:
- To review the structure, biological functions, and disease relevance of A3B.
- To summarize current research on A3B inhibitors.
- To discuss the design requirements and mechanisms of action for A3B inhibitors.
Main Methods:
- Literature review of A3B structure, function, and disease association.
- Systematic summary of reported A3B inhibitors.
- Analysis of inhibitor design principles and modes of action.
Main Results:
- A3B's dual role in viral defense and oncogenesis is highlighted.
- Aberrant A3B expression correlates with aggressive tumor phenotypes and drug resistance.
- Oligonucleotide and allosteric inhibitors demonstrate promising therapeutic potential.
Conclusions:
- A3B is a significant factor in cancer progression and drug resistance.
- Targeting A3B offers a potential strategy for cancer therapy.
- Further development of selective A3B inhibitors is warranted.
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