Introduction: Topoisomerase (topo) II inhibitors continue to represent a promising approach in anticancer therapy, although their clinical application is hampered by drug resistance and dose limiting toxicities.
Area covered: We performed a critical analysis of patent literature from January 2016 to January 2025 on topo II inhibitors in oncology using the online databases Espacenet, Wipo, and Google patent.
Expert opinion: Substantial progress in the development of novel topo II inhibitors through synthetic chemistry, natural product isolation, molecular modification, and in silico screening was recorded. These compounds belong to different chemical classes and mainly exhibit in vitro cytotoxicity in a low micromolar range, comparable to or greater than that induced by clinically established topo II inhibitors such as doxorubicin and etoposide. Some patented compounds showed catalytic inhibition of topo II enzyme, offering a safer and more effective alternative to topo II poisons. Despite encouraging in vitro data, only a few patents provide in vivo data or mechanistic insights, and none have progressed to clinical trials, highlighting a gap between preclinical innovation and clinical translation. Future research needs advancing in clinical development to fully realize the therapeutic potential of next-generation topo II inhibitors.
Keywords: Anticancer therapy; catalytic inhibitors; patent; topoisomerase II; topoisomerase II inhibitors.