AR-67 is a third-generation camptothecin analogue that was being developed by Arno Therapeutics for the treatment of cancer, but has been discontinued. AR-67 had been in phase II clinical trials for the treatment of glioblastoma multiforme and myelodysplastic syndrome. AR-67is a synthetic, highly lipophilic derivative of camptothecin, with potential antineoplastic and radiosensitizing activities. AR-67 binds to and stabilizes the topoisomerase I-DNA covalent complex, inhibiting the religation of topoisomerase I-mediated single-stranded DNA breaks and producing lethal double-stranded DNA breaks when encountered by the DNA replication machinery; inhibition of DNA replication and apoptosis follow. Camptothecin readily undergoes hydrolysis at physiological pH, changing its conformation from the active lactone structure to an inactive carboxylate form. Modifications on the E ring of camptothecin prevent binding of human serum albumin, which prefers the inactive carboxylate form, thereby enhancing the stability of the active lactone structure and resulting in prolonged agent activity.