One-Handed Molecule Disarms the Cell-Death Trigger BAX
- Research highlight on a stereoselective, cysteine-reactive molecule that locks the pro-apoptotic protein BAX into an inactive shape, blocking programmed cell death.
- Optimization yielded a lead compound suitable for in vivo dosing that limited liver-cell death and preserved organ function in a mouse model of acute liver injury.
- It also protected stem-cell-derived motor neurons from healthy and ALS-patient donors, pointing to wider relevance in neurodegenerative disease.
💡 Points
This is the kind of binding-mode elegance you rarely see survive contact with an animal model — a stereoselective, cysteine-directed covalent lock on BAX's inactive conformation, in a target class that's almost entirely been reversible PPI chemistry. Holding up in both a liver-injury model and ALS-donor motor neurons argues for real engagement, not a lucky crosslinker; I'd still want the off-target cysteine panel.