Multi-target kinase-IN-10

Multi-target kinase-IN-10 (Compound 6l) is an orally active, brain-penetrant, selective, reversible, and competitive MAO-B inhibitor with an IC50 of 0.0053 μM. It competes with substrates for binding to the active site of MAO-B, chelates Cu2+ ions, inhibits Cu2+-induced ROS production, and decreases the release of NO, TNF-α, and IL-1β. Multi-target kinase-IN-10 shows potential for improving Parkinson's disease.

MAO-B:0.0053 μM

Multi-target kinase-IN-10 is a potent and selective inhibitor of MAO-B, with an IC50 of 0.0053 μM and a selectivity index greater than 1904.7. In concentrations ranging from 0.5 to 10.0 μM, Multi-target kinase-IN-10 dose-dependently inhibits the release of NO, TNF-α, and IL-1β induced by LPS in BV-2 microglial cells. Additionally, at concentrations between 2.5 and 10.0 μM, it dose-dependently reduces ROS production in LPS-induced BV-2 microglial cells, achieving inhibition rates of 18.9% at 2.5 μM and 41.7% at 10.0 μM.

Multi-target kinase-IN-10 (administered via gavage daily at a dose of 7.5-37.5 mg/kg) significantly enhances behavioral recovery and striatal dopamine levels in subacute Parkinson's disease mice induced by MPTP. It also reduces oxidative stress, alleviates neuroinflammation, and protects dopaminergic neurons.