FL77-32

FL77-32 is a small molecule derived from the FL118 anticancer drug platform, developed through medicinal chemistry synthesis involving heterocyclic ring modifications. It demonstrates potent antitumor activity, particularly against malignant pleural mesothelioma (MPM), by inducing p53 and p21 accumulation, Rb dephosphorylation, G1/G0 cell cycle arrest, senescence, and apoptosis in cancer cells. FL77-32 potently downregulates anti-apoptotic proteins including survivin (BIRC5), Mcl-1, Bcl-2, and Bcl-XL while upregulating pro-apoptotic factors like PUMA, cleaved caspase-3, and PARP; it also reduces DDX5 expression, overlapping but exceeding the mechanism of parent compound FL118. In vivo, it shows superior efficacy to the pemetrexed-cisplatin standard in MPM xenograft models at low doses (1.25-7.5 mg/kg), positioning it as a promising monotherapy candidate for clinical development in aggressive cancers like MPM, osteosarcoma, and others.