F14512

F14512 is a novel anticancer agent derived from etoposide, with a unique structure featuring a spermine moiety replacing the typical C4 glycosidic group. This modification enables selective uptake into cancer cells via the polyamine transport system, which is frequently overactivated in cancers[1][5][3]. Mechanistically, F14512 acts as a potent topoisomerase II poison by stabilizing the topoisomerase II–DNA cleavable complex, inducing DNA double-strand breaks and promoting cytotoxicity with enhanced activity compared to etoposide. Unlike etoposide, F14512 demonstrates activity even in the absence of ATP and binds DNA more tightly[1]. It triggers both cellular senescence and apoptosis in cancer models, without promoting autophagy[7][5]. The drug is primarily under investigation for hematologic cancers, including acute myeloid leukemia (AML), and has shown strong preclinical and early clinical efficacy, including benefits in multidrug-resistant and P-glycoprotein-overexpressing lymphoma models[2][6][9].

Other names

F14512F-14512F 14512