A-1684909

A-1684909 is a small molecule activator of the eukaryotic translation initiation factor 2B (eIF2B) complex, developed by AbbVie for the treatment of vanishing white matter disease (VWMD) and Cree leukoencephalopathy. VWMD is a rare, progressive leukodystrophy caused by biallelic mutations in any of the five subunits of eIF2B, which is the master regulator of protein synthesis and the integrated stress response (ISR). These mutations reduce eIF2B's guanine nucleotide exchange factor (GEF) activity, leading to an aberrant, chronic activation of the ISR that is toxic to astrocytes and oligodendrocytes. A-1684909 functions as a positive allosteric modulator that stabilizes the decameric form of eIF2B, thereby enhancing its enzymatic activity and restoring translational control. By suppressing the pathological ISR, A-1684909 aims to preserve white matter integrity and slow neurological deterioration in affected patients.

Other names

eIF2B activatoreIF-2B activatoreIF 2B activator