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5 results for “Reactive metabolites”
Data from: Liquid chromatography-tandem mass spectrometry metabolic profiling of nazartinib reveals the formation of unexpected reactive metabolites
Nazartinib (EGF816, NZB) is a promising third-generation human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This novel irreversible mutant-selective EGFR inhibitor targets EGFR containing both the resistance mutation (T790M) and the activating mutations (L858R and Del19), while it does not affect wild-type EGFR. However, the metabolic pathway and bioactivation mechanisms of NZB are still unexplored. Thus, using liquid chromatography-tandem mass spectrometry, we screened for products of NZB metabolism formed in vitro by human liver microsomal preparations and investigated the formation of reactive intermediates using potassium cyanide as a nucleophile trap. Unexpectedly, the azepane ring was not bioactivated. Instead, the carbon atom between the aliphatic linear tertiary amine and electron-withdrawing system (butenoyl amide group) was bioactivated, generating iminium intermediates as reactive species. Six NZB phase I metabolites, formed by hydroxylation, oxidation, and N-demethylation, were characterized. Moreover, two reactive iminium ions were characterized and their corresponding bioactivation mechanisms were proposed. Based on our results, we speculate that bioactivation of NZB can be blocked by small sterically hindering groups, isosteric replacement, or a spacer. This approach might reduce the toxicity of NZB by avoiding the generation of reactive species.
Data from: Liquid chromatography-tandem mass spectrometry metabolic profiling of nazartinib reveals the formation of unexpected reactive metabolites
Open the record for dataset details and reuse information.
Evaluation of Reactive Oxygen Metabolites in the Value of COPD
ClinicalTrials.gov study NCT02297633. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Application of a Rat Liver Drug Bioactivation Transcriptional Response Assay Early in Drug Development that informs Chemically Reactive Metabolite formation
GEO Series GSE149734. Rattus norvegicus. 241 samples. Type: Expression profiling by array.
S-lactoyl modification of KEAP1 by a reactive glycolytic metabolite activates NRF2 signaling
GEO Series GSE230577. Homo sapiens. 6 samples. Type: Expression profiling by high throughput sequencing.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.