Dual-target carbonic anhydrase inhibitors in cancer therapy: progress, challenges, and opportunities

IF 3.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Research Pub Date : 2026-08-17 DOI:10.1007/s00044-026-03605-7

Meizhen Luo, Yong Wang, Yinmei Xia, Qin-Min Wang, Jifa Zhang, Lianhai Shan

{"title":"Dual-target carbonic anhydrase inhibitors in cancer therapy: progress, challenges, and opportunities","authors":"Meizhen Luo, Yong Wang, Yinmei Xia, Qin-Min Wang, Jifa Zhang, Lianhai Shan","doi":"10.1007/s00044-026-03605-7","DOIUrl":null,"url":null,"abstract":"<div><p>Carbonic anhydrases (CA) are metalloenzymes that mediate diverse physiological and pathological processes, including pH, metabolism, and electrolyte balance, making them key therapeutic targets. Although numerous carbonic anhydrase inhibitors are clinically used for glaucoma, mountain sickness, hypoxic tumors and epilepsy, their efficacy is often limited by systemic toxicity, drug resistance, and poor activity against multifactorial diseases. Multi-target combination therapy, particularly via dual-target agents, offers a promising strategy to overcome these hurdles. Given the synergistic relationships between CA and epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR) and histone deacetylase (HDAC), among other common drug targets, dual-target carbonic anhydrase inhibitors (CAIs) hold great potential to circumvent current limitations and enhance treatment outcomes. This review summarizes recent progress in dual-target CAIs, emphasizing design strategies, structure-activity relationships (SAR), and translational challenges, and provides a theoretical foundation and innovative perspectives for next-generation CA-directed therapies.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 9","pages":"1626 - 1666"},"PeriodicalIF":3.5000,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicinal Chemistry Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00044-026-03605-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Carbonic anhydrases (CA) are metalloenzymes that mediate diverse physiological and pathological processes, including pH, metabolism, and electrolyte balance, making them key therapeutic targets. Although numerous carbonic anhydrase inhibitors are clinically used for glaucoma, mountain sickness, hypoxic tumors and epilepsy, their efficacy is often limited by systemic toxicity, drug resistance, and poor activity against multifactorial diseases. Multi-target combination therapy, particularly via dual-target agents, offers a promising strategy to overcome these hurdles. Given the synergistic relationships between CA and epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR) and histone deacetylase (HDAC), among other common drug targets, dual-target carbonic anhydrase inhibitors (CAIs) hold great potential to circumvent current limitations and enhance treatment outcomes. This review summarizes recent progress in dual-target CAIs, emphasizing design strategies, structure-activity relationships (SAR), and translational challenges, and provides a theoretical foundation and innovative perspectives for next-generation CA-directed therapies.

查看原文本刊更多论文

癌症治疗中的双靶点碳酸酐酶抑制剂：进展、挑战和机遇。

碳酸酐酶（CA）是一种金属酶，介导多种生理和病理过程，包括pH、代谢和电解质平衡，使其成为关键的治疗靶点。尽管临床上有许多碳酸酐酶抑制剂用于青光眼、高原病、缺氧肿瘤和癫痫，但它们的疗效往往受到全身毒性、耐药性和对多因素疾病活性差的限制。多靶点联合治疗，特别是通过双靶点药物，为克服这些障碍提供了一个有希望的策略。鉴于CA与表皮生长因子受体（EGFR）、血管内皮生长因子受体（VEGFR）和组蛋白去乙酰化酶（HDAC）以及其他常见药物靶点之间的协同关系，双靶点碳酸酐酶抑制剂（CAIs）具有很大的潜力，可以克服目前的局限性，提高治疗效果。本文综述了双靶点CAIs的最新进展，强调了设计策略、结构-活性关系（SAR）和转化挑战，并为下一代ca导向治疗提供了理论基础和创新视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Medicinal Chemistry Research 医学-医药化学

CiteScore

4.70

自引率

3.80%

发文量

162

审稿时长

5.0 months

期刊介绍： Medicinal Chemistry Research (MCRE) publishes papers on a wide range of topics, favoring research with significant, new, and up-to-date information. Although the journal has a demanding peer review process, MCRE still boasts rapid publication, due in part, to the length of the submissions. The journal publishes significant research on various topics, many of which emphasize the structure-activity relationships of molecular biology.