Recent advances in combretastatin A-4 codrugs for cancer therapy

CA4 is a potent microtubule polymerization inhibitor and vascular disrupting agent. However, the in vivo effi-ciency 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 anti -vascular 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.

Automated summary

CA4 phosphate (CA4P) has been developed to improve the water solubility and in vivo efficiency of CA4. However, clinical trials evaluating CA4P as a vascular disrupting agent showed unfavorable results. The design of CA4-based codrugs is being explored to improve therapeutic efficacy and achieve targeted delivery to cancer tissues.