{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13(7)"],"submitter":["Huang J"],"funding":["Anticancer Bioscience"],"pubmed_abstract":["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."],"journal":["ACS medicinal chemistry letters"],"pagination":["1091-1098"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9290026"],"repository":["biostudies-literature"],"pubmed_title":["Discovery and Optimization of Seven-Membered Lactam-Based Compounds to Phenocopy the Inhibition of the Aurora Kinase B."],"pmcid":["PMC9290026"],"pubmed_authors":["Li H","Li J","Reddy MC","Huang J","Zhang J","Shi Q","Zhang S","Yang D","Yang C","Choudhry N","Yan Z","Kalashova J","Nimishetti N","Gopala SG"],"additional_accession":[]},"is_claimable":false,"name":"Discovery and Optimization of Seven-Membered Lactam-Based Compounds to Phenocopy the Inhibition of the Aurora Kinase B.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-04T13:52:43.167Z","creation":"2025-04-04T13:52:43.167Z"},"accession":"S-EPMC9290026","cross_references":{"pubmed":["35859866"],"doi":["10.1021/acsmedchemlett.2c00098"]}}