biostudies-literatureGopinath PMinistry of Science,Technology and space7079-7086https://www.ebi.ac.uk/biostudies/studies/S-EPMC5355956biostudies-literatureUnknown7(12)Recent studies have suggested that selective targeting of overexpressed enzymes in cancer cells by small molecules that induce the formation of reactive oxygen species (ROS) could be a viable approach in cancer therapy. One such example is the inactivation of ubiquitin specific protease-2 (USP2)-an emerging drug target to combat prostate cancer-by β-lapachone, which has been identified to involve oxidation of the catalytic cysteine's thiol residue to sulfinic acid. A rational design of β-lapachone analogs with improved activity requires a much better understanding of the variables that determine ROS production by this class of molecules. This crucial aspect was addressed <i>via</i> modulation of its 1,2-naphthoquinone scaffold and establishment of a structure/activity relationship, regardiChemical scienceUnderstanding and predicting the potency of ROS-based enzyme inhibitors, exemplified by naphthoquinones and ubiquitin specific protease-2.PMC53559562021900Brik AGopinath PMahammed AOhayon SGross ZfalseUnderstanding and predicting the potency of ROS-based enzyme inhibitors, exemplified by naphthoquinones and ubiquitin specific protease-2.Recent studies have suggested that selective targeting of overexpressed enzymes in cancer cells by small molecules that induce the formation of reactive oxygen species (ROS) could be a viable approach in cancer therapy. One such example is the inactivation of ubiquitin specific protease-2 (USP2)-an emerging drug target to combat prostate cancer-by β-lapachone, which has been identified to involve oxidation of the catalytic cysteine's thiol residue to sulfinic acid. A rational design of β-lapachone analogs with improved activity requires a much better understanding of the variables that determine ROS production by this class of molecules. This crucial aspect was addressed <i>via</i> modulation of its 1,2-naphthoquinone scaffold and establishment of a structure/activity relationship, regardi2016-01-01T00:00:00Z2016 Dec2025-05-29T19:21:15.2Z2025-05-29T19:21:15.2ZS-EPMC53559562845114310.1039/c6sc02758j