Alverez Celeste, Bulfer Stacie L, Chakrasali Ramappa, Chimenti Michael S, Deshaies Raymond J, Green Neal, Kelly Mark, LaPorte Matthew G, Lewis Taber S, Liang Mary, Moore William J, Neitz R Jeffrey, Peshkov Vsevolod A, Walters Michael A, Zhang Feng, Arkin Michelle R, Wipf Peter, Huryn Donna M
Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States; University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Department of Pharmaceutical Chemistry, Small Molecule Discovery Center, University of California , San Francisco, California 94158, United States.
ACS Med Chem Lett. 2015 Dec 22;7(2):182-7. doi: 10.1021/acsmedchemlett.5b00396. eCollection 2016 Feb 11.
A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts.
一项旨在发现p97 ATP酶活性抑制剂的高通量筛选鉴定出一种与该蛋白变构位点结合的吲哚酰胺。药物化学优化提高了其效力和溶解度。吲哚酰胺3是一种新型非竞争性抑制剂，具有优异的物理和药学性质，可作为药物研发工作的起点。
