(14S)-14β-(1-(2-morpholinoethyl)-1H-indazol-5-ylamino)mthylepitriptolide (LLDT-288) was a novel C14β-heterocycle aminomethyl substituent triptolide analogue, which showed comparable cytotoxicity to triptolide. Here we demonstrated that LLDT-288 displayed broad-spectrum, potent antitumor activity, effectively against drug-resistance cancer cells, and induced apoptosis in vitro, but exerted low toxicity. Moreover, it exhibited a remarkable microsomal stability, and showed no inhibitory effects on different cytochrome P450 isoforms. In vivo, orally administration of LLDT-288 exhibits promising efficacy in human prostate (PC-3) xenograft mice model with obviously low toxicity. Further, the in vivo metabolic studies suggested that LLDT-288 was extensively metabolized in rats and mainly excreted in the form of metabolites in the feces.
