ITH12410/SC058: A New Neuroprotective Compound with Potential in the Treatment of Alzheimer’s Disease Alejandro Romero Javier Egea Gema C. González-Muñoz M Martı́n de Saavedra Laura del Barrio María Isabel Rodríguez-Franco Santiago Conde Manuela G. López Mercedes Villarroya Cristóbal de los Ríos 10.1021/cn500131t.s001 https://acs.figshare.com/articles/journal_contribution/ITH12410_SC058_A_New_Neuroprotective_Compound_with_Potential_in_the_Treatment_of_Alzheimer_s_Disease/2254231 The neuroprotective profile of the dibenzothiadiazepine ITH12410/SC058 (2-chloro-5,6-dihydro-5,6-diacetyldibenzo­[<i>b</i>,<i>f</i>]­[1,4,5]­thiadiazepine) against several neurotoxicity models related to neurodegenerative diseases is herein described. ITH12410/SC058 protected SH-SY5Y cells against the loss of cell viability elicited by amyloid beta peptide and okadaic acid, a selective inhibitor of phosphoprotein phosphatase 2A that induces neurofibrillary tangle formation. Furthermore, ITH12410/SC058 is neuroprotective against several in vitro models of oxidative stress, that is, H<sub>2</sub>O<sub>2</sub> exposure or incubation with rotenone plus oligomycin A in SH-SY5Y cells, and oxygen and glucose deprivation followed by reoxygenation in rat hippocampal slices. By contrast, ITH12410/SC058 was unable to significantly protect SH-SY5Y neuroblastoma cells against the toxicity elicited by Ca<sup>2+</sup> overload. Our results confirm the hypothesis that the dibenzothiadiazepine ITH12410/SC058 features its neuroprotective actions in a multitarget fashion, and is a promising drug for the treatment of neurodegenerative diseases. 2014-09-17 00:00:00 5Y neurofibrillary tangle formation neuroprotective H 2O exposure neurodegenerative diseases amyloid beta peptide ITH phosphoprotein phosphatase 2 rat hippocampal slices