@article {Chen231, author = {Yuanyuan Chen and Hong Tang and William Seibel and Ruben Papoian and Ki Oh and Xiaoyu Li and Jianye Zhang and Marcin Golczak and Krzysztof Palczewski and Philip D. Kiser}, title = {Identification and Characterization of Novel Inhibitors of Mammalian Aspartyl Aminopeptidase}, volume = {86}, number = {2}, pages = {231--242}, year = {2014}, doi = {10.1124/mol.114.093070}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin signaling and endosome trafficking, but its precise biologic roles remain incompletely defined. We performed a high-throughput screen of \~{}25,000 small molecules to identify inhibitors of DNPEP for use as tools to study its biologic functions. Twenty-three confirmed hits inhibited DNPEP-catalyzed hydrolysis of angiotensin II with micromolar potency. A counter screen against glutamyl aminopeptidase (ENPEP), an enzyme with substrate specificity similar to that of DNPEP, identified eight DNPEP-selective inhibitors. Structure-activity relationships and modeling studies revealed structural features common to the identified inhibitors, including a metal-chelating group and a charged or polar moiety that could interact with portions of the enzyme active site. The compounds identified in this study should be valuable tools for elucidating DNPEP physiology.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/86/2/231}, eprint = {https://molpharm.aspetjournals.org/content/86/2/231.full.pdf}, journal = {Molecular Pharmacology} }