BC1464 (BC 1464) is a small molecule inhibitor of ubiquitin E3 ligase receptor component FBXO7, efficiently decreases the interaction between FBXO7 and PINK1, increases cellular PINK1 concentrations and activities.
BC1464 stabilized PINK1 and increased PINK1 protein levels in cells in a dose-dependent manner through inhibiting FBXO7.
BC1464 (10 ng/mL) potently blocked LPS-stimulated release of the proinflammatory cytokine TNF-α in human PBMCs, also selectively increased PINK1 protein levels and inhibited proinflammatory TNF-α release in response to endotoxin in human lung explants.
BC1464 (5 mg/kg, i.p.) significantly decreased lavage protein, cell numbers, cytokine levels, and tissue infiltrates with restoration of PINK1 levels in experimental mouse pneumonia.
BC1464 stabilized PINK1 expression in the presence of CHX in neuronal cells with IC50 of 5.2 μg/mL.
BC1464 significantly decreased MPP+-elicited injury in human SH-SY5Y cells, exhibited significant protection against Parkinsonian toxin 6-hydroxydopamine (6-OHDA) in fibroblasts from Parkinson's disease patients.