Journal article
A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection
Abstract
Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between …
Authors
Niu X; Brahmbhatt H; Mergenthaler P; Zhang Z; Sang J; Daude M; Ehlert FGR; Diederich WE; Wong E; Zhu W
Journal
Cell Chemical Biology, Vol. 24, No. 4, pp. 493–506.e5
Publisher
Elsevier
Publication Date
April 2017
DOI
10.1016/j.chembiol.2017.03.011
ISSN
2451-9456
Associated Experts
Fields of Research (FoR)
Medical Subject Headings (MeSH)
AnimalsApoptosisBinding SitesCells, CulturedFemaleGlutamic AcidHCT116 CellsHumansLiposomesMaleMiceMitochondrial MembranesNeuronsNeuroprotective AgentsPermeabilityProtein MultimerizationProtein Structure, TertiaryRecombinant ProteinsSmall Molecule LibrariesStructure-Activity Relationshipbcl-2 Homologous Antagonist-Killer Proteinbcl-2-Associated X Protein