Artikel ; Online: Discovery of a Chemical Probe to Study Implications of BPTF Bromodomain Inhibition in Cellular and in vivo Experiments.
2023 Band 18, Heft 6, Seite(n) e202200686
Abstract: The bromodomain and PHD-finger containing transcription factor (BPTF) is part of the nucleosome remodeling factor (NURF) complex and has been implicated in multiple cancer types. Here, we report the discovery of a potent and selective chemical probe ... ...
Abstract | The bromodomain and PHD-finger containing transcription factor (BPTF) is part of the nucleosome remodeling factor (NURF) complex and has been implicated in multiple cancer types. Here, we report the discovery of a potent and selective chemical probe targeting the bromodomain of BPTF with an attractive pharmacokinetic profile enabling cellular and in vivo experiments in mice. Microarray-based transcriptomics in presence of the probe in two lung cancer cell lines revealed only minor effects on the transcriptome. Profiling against a panel of cancer cell lines revealed that the antiproliferative effect does not correlate with BPTF dependency score in depletion screens. Both observations and the multi-domain architecture of BPTF suggest that depleting the protein by proteolysis targeting chimeras (PROTACs) could be a promising strategy to target cancer cell proliferation. We envision that the presented chemical probe and the related negative control will enable the research community to further explore scientific hypotheses with respect to BPTF bromodomain inhibition. |
---|---|
Mesh-Begriff(e) | Animals ; Mice ; Cell Proliferation ; Gene Expression Regulation ; Lung Neoplasms ; Nuclear Proteins/metabolism ; Transcription Factors/metabolism |
Chemische Substanzen | Nuclear Proteins ; Transcription Factors ; fetal Alzheimer antigen |
Sprache | Englisch |
Erscheinungsdatum | 2023-02-06 |
Erscheinungsland | Germany |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2218496-X |
ISSN | 1860-7187 ; 1860-7179 |
ISSN (online) | 1860-7187 |
ISSN | 1860-7179 |
DOI | 10.1002/cmdc.202200686 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Volltext online
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
Zs.A 6280: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.