PELSA dataset for supporting the discovery of anti-apoptotic BAX inhibitors

ABSTRACT: BAX is a critical regulator of the apoptosis cascade and its abnormal activation can lead to the development of disease including cardiovascular and neurodegenerative diseases. Therefore, BAX represents an attractive target for the pharmacological inhibition of pathological cell death. Based on a focused screening approach of containing FDA-approved drugs, we identified and modified several approved or in clinical EGFR kinase inhibitors with potential activity against BAX. Systematic modifications to the core structure were performed, allowing us to elucidate how structural modifications influence biological activity and leading to a comprehensive structure-activity relationship (SAR) on BAX inhibition. The developed quinazole series has favorable drug-like properties, further improved BAX inhibitory activity in vitro and in cellular settings while no cytotoxicity and significantly reduced EGFR kinase activity was achieved. This series therefore represents a promising starting point for the development of improved and potentially therapeutic BAX inhibitors. PELSA was performed to confirm NMR data and docking studies for identifying the binding site of the novel inhibitors on BAX.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney Epithelial Cell, Cell Culture

SUBMITTER: Max Ruwolt  

LAB HEAD: Marc Nazaré

PROVIDER: PXD075850 | Pride | 2026-11-07

REPOSITORIES: Pride