CA4 is a potent microtubule polymerization inhibitor and vascular disrupting agent. However, the in vivo efficiency of CA4 is limited owing to its poor pharmacokinetics resulting from its high lipophilicity and low water solubility. To improve the water solubility, CA4 phosphate (CA4P) has been developed and shows potent antivascular and antitumor effects. CA4P had been evaluated as a vascular disrupting agent in previousc linical trials. However, it had been discontinued due to the lack of a meaningful improvement in progression-free survival and unfavorable partial response data. Codrug is a drug design approach to chemically bind two or more drugs to improve therapeutic efficiency or decrease adverse effects. This review describes the progress made over the last twenty years in developing CA4-based codrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues. It also discusses the existing problems and the developmental prospects of CA4 codrugs.

CA4 是一种有效的微管聚合抑制剂和血管破坏剂。然而，体内CA4 的高亲脂性和低水溶性导致其药代动力学较差，因此其效率受到限制。为了提高水溶性，已开发出 CA4 磷酸盐 (CA4P)，并显示出有效的抗血管和抗肿瘤作用。在之前的临床试验中，CA4P 已被评估为血管破坏剂。然而，由于无进展生存期缺乏有意义的改善和不利的部分反应数据，它已经停止。联合药物是一种药物设计方法，可以化学结合两种或多种药物以提高治疗效率或减少副作用。这篇综述描述了过去 20 年来在开发基于 CA4 的联合药物以改善治疗概况和实现对癌组织的靶向递送方面取得的进展。