Pt(IV) Prodrug Photoactivation: A Promising Strategy for Cancer Therapy.

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current protein & peptide science Pub Date : 2024-06-25 DOI:10.2174/0113892037297416240525155628

Lingkai Tang, Yafei Luo, Wenqin Luo, Guangzhou Sun, Yu Jiang, Zhigang Zhang, Xinru Yue, Siyao Li, Li Liang, Wei Liu, Jianping Hu

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Abstract

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance. The controlled conversion of Pt(IV) prodrugs into Pt(II) agents at the tumor site has been extensively explored internationally. In this review, Pt(IV) prodrug modification strategies are first summarized, next the development of the predominant external and internal photosensitizers is listed. Finally, three representative photoreduction mechanisms and strategies for developing corresponding Pt(IV) prodrugs are discussed. This work provides constructive instruction for the subsequent molecular design of Pt(IV) prodrugs.

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铂(IV)原药光活化：一种前景广阔的癌症治疗策略

包括顺铂、卡铂和奥沙利铂在内的铂（II）类药物在癌症治疗中取得了显著的临床疗效。然而，非特异性活化和耐药性等各种不利因素极大地阻碍了它们的临床应用。与铂(II)类药物相比，铂(IV)化合物中的轴向配体可以改善药物动力学特性、选择性和生物活性，实现 DNA 交联之外的另一种细胞毒性机制，并部分克服耐药性。在肿瘤部位将铂(IV)原药可控地转化为铂(II)制剂已在国际上得到广泛探索。在这篇综述中，首先总结了铂(IV)原药的修饰策略，然后列举了主要的内外光敏剂的发展情况。最后，讨论了三种具有代表性的光诱导机制以及开发相应铂(IV)原药的策略。这项工作为后续铂(IV)原药的分子设计提供了建设性指导。.

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来源期刊

Current protein & peptide science 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.