biostudies-literatureUnknown13(7)Huang JAnticancer BioscienceWe used mechanism-informed phenotypic screening to identify and optimize compounds that phenocopy the genetic depletion of the mitotic aurora kinase B (AURKB) kinase. After assaying nine aryl fused seven-membered lactam compounds, we identified a hit compound <b>6a</b> that was subsequently optimized to five lead compounds with low nanomolar activity, represented by the lead compound <b>6v</b> (19 nM). With excellent drug-like properties, these compounds reproduced the loss of function in phenotypes of AURKB and exhibited potent cytotoxic activities in various cancer cell lines. Collectively, these data support that seven-membered lactam-based analogs might be valuable for further development as a new type of antimitotic agents for the treatment of cancer.ACS medicinal chemistry letters1091-1098https://www.ebi.ac.uk/biostudies/studies/S-EPMC9290026biostudies-literatureDiscovery and Optimization of Seven-Membered Lactam-Based Compounds to Phenocopy the Inhibition of the Aurora Kinase B.PMC9290026Li HLi JReddy MCHuang JZhang JShi QZhang SYang DYang CChoudhry NYan ZKalashova JNimishetti NGopala SGfalseDiscovery and Optimization of Seven-Membered Lactam-Based Compounds to Phenocopy the Inhibition of the Aurora Kinase B.We used mechanism-informed phenotypic screening to identify and optimize compounds that phenocopy the genetic depletion of the mitotic aurora kinase B (AURKB) kinase. After assaying nine aryl fused seven-membered lactam compounds, we identified a hit compound <b>6a</b> that was subsequently optimized to five lead compounds with low nanomolar activity, represented by the lead compound <b>6v</b> (19 nM). With excellent drug-like properties, these compounds reproduced the loss of function in phenotypes of AURKB and exhibited potent cytotoxic activities in various cancer cell lines. Collectively, these data support that seven-membered lactam-based analogs might be valuable for further development as a new type of antimitotic agents for the treatment of cancer.2022-01-01T00:00:00Z2022 Jul2025-04-04T13:52:43.167Z2025-04-04T13:52:43.167ZS-EPMC92900263585986610.1021/acsmedchemlett.2c00098