TP300

TP300 is a synthetic camptothecin analogue and a highly selective small molecule inhibitor of topoisomerase I (Top1). Developed by Chugai Pharmaceutical, it functions as a prodrug; its active form is TP3076, which is further metabolized into the active metabolite TP3011. By targeting Top1, an enzyme essential for DNA replication and transcription, TP300 stabilizes the DNA-Top1 cleavage complex, preventing DNA re-ligation and causing lethal double-strand breaks. It has been evaluated in Phase I and Phase II clinical trials as a monotherapy for advanced gastric cancer and gastroesophageal junction (GOJ) adenocarcinoma. Clinical administration involves a 1-hour intravenous infusion every three weeks, with neutropenia identified as a significant dose-limiting toxicity.