Vodobatinib, a potent, orally bioavailable brain-penetrating inhibitor of c-Abl as a potential neuroprotective agent for treatment of Parkinson disease

Background:Preclinical evidence suggests that c-Abl is critical for pathogenesis of Parkinson Disease (PD). Vodobatinib is a potent, orally bioavailable inhibitor of c-Abl currently being evaluated in patients with PD in the PROSEEK clinical trial. Nilotinib, a multikinase inhibitor of c-Abl, was recently shown to be unsuccessful in slowing PD progression (Simuni et al. 2021). This failure of nilotinib at its maximally permissible dose of 300mg was attributed to insufficient brain penetration because the concentration of nilotinib in the CSF was found to be 7-fold lower than its IC50 for c-Abl.
Source: Parkinsonism and Related Disorders - Category: Neurology Authors: Source Type: research