{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Skwarska A"],"funding":["Medical Research Council","EPSRC","Engineering and Physical Sciences Research Council"],"pagination":["1258-1270.e13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8460716"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(9)"],"pubmed_abstract":["Tumor hypoxia is associated with therapy resistance and poor patient prognosis. Hypoxia-activated prodrugs, designed to selectively target hypoxic cells while sparing normal tissue, represent a promising treatment strategy. We report the pre-clinical efficacy of 1-methyl-2-nitroimidazole panobinostat (NI-Pano, CH-03), a novel bioreductive version of the clinically used lysine deacetylase inhibitor, panobinostat. NI-Pano was stable in normoxic (21% O<sub>2</sub>) conditions and underwent NADPH-CYP-mediated enzymatic bioreduction to release panobinostat in hypoxia (<0.1% O<sub>2</sub>). Treatment of cells grown in both 2D and 3D with NI-Pano increased acetylation of histone H3 at lysine 9, induced apoptosis, and decreased clonogenic survival. Importantly, NI-Pano exhibited growth delay effec"],"journal":["Cell chemical biology"],"pubmed_title":["Development and pre-clinical testing of a novel hypoxia-activated KDAC inhibitor."],"pmcid":["PMC8460716"],"funding_grant_id":["MR/N009460/1","EP/S019901/1"],"pubmed_authors":["Conway SJ","Martin J","Odyniec ML","Skwarska A","Calder EDD","Mistry IN","Sneddon D","Folkes LK","Bolland H","Hammond EM"],"additional_accession":[]},"is_claimable":false,"name":"Development and pre-clinical testing of a novel hypoxia-activated KDAC inhibitor.","description":"Tumor hypoxia is associated with therapy resistance and poor patient prognosis. Hypoxia-activated prodrugs, designed to selectively target hypoxic cells while sparing normal tissue, represent a promising treatment strategy. We report the pre-clinical efficacy of 1-methyl-2-nitroimidazole panobinostat (NI-Pano, CH-03), a novel bioreductive version of the clinically used lysine deacetylase inhibitor, panobinostat. NI-Pano was stable in normoxic (21% O<sub>2</sub>) conditions and underwent NADPH-CYP-mediated enzymatic bioreduction to release panobinostat in hypoxia (<0.1% O<sub>2</sub>). Treatment of cells grown in both 2D and 3D with NI-Pano increased acetylation of histone H3 at lysine 9, induced apoptosis, and decreased clonogenic survival. Importantly, NI-Pano exhibited growth delay effec","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-05-08T16:39:43.121Z","creation":"2022-02-11T11:30:15.922Z"},"accession":"S-EPMC8460716","cross_references":{"pubmed":["33910023"],"doi":["10.1016/j.chembiol.2021.04.004"]}}