TP-P1

TP-P1 is a novel, water-soluble, rapid-release prodrug of triptolide, developed by inserting glycolic acid as a linker between triptolide and a cyclic amino acid. This modification aims to improve its drug-like properties, including enhanced water solubility and accelerated release of the active triptolide into plasma, while maintaining safety. Preclinical studies in mouse models of human acute myeloid leukemia (AML) demonstrated TP-P1's high efficacy, showing significant reduction of xenograft tumors at doses as low as 25 μg/kg and complete elimination at 100 μg/kg. TP-P1 also exhibited superior plasma release rates and synthetic yield compared to Minnelide, another water-soluble triptolide prodrug in clinical trials. Furthermore, TP-P1 was found to significantly enhance the efficacy of FLT3 inhibitors in AML treatment.