PBT434 mesylate

PBT434 methanesulfonate is a potent, orally active and cross the blood-brain barrier α-synuclein aggregation inhibitor. PBT434 methanesulfonate can be used as a iron chelator and modulates transcellular iron trafficking. PBT434 methanesulfonate inhibits iron-mediated redox activity and iron-mediated aggregation of α-synuclein. PBT434 methanesulfonate prevents the loss of substantia nigra pars compacta neurons (SNpc). PBT434 methanesulfonate has the potential for the research of Parkinson’s disease (PD).

PBT434 methanesulfonate (0-20 µM; 3 h) significantly inhibits H₂O₂ production by iron and significantly reduces the rate of Fe-mediated aggregation of α-synuclein^[1].
PBT434 methanesulfonate (0-100 µM; 24 h) shows no cytotoxic effects on brain microvascular endothelial cells^[2].
PBT434 methanesulfonate (20 µM; 24 h) incrases the expression of total TfR, Cp protein level in hBMVEC^[2].

PBT434 methanesulfonate (30 mg/kg; p.o.; daily for 21 days) significantly preserved neuron numbers in the 6-OHDA intoxication model and shows significantly fewer rotations in the L-DOPA model, significantly reducing SNpc neuronal loss in the MPTP model^[1].

References:
[1]. Finkelstein DI, et al. The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease. Acta Neuropathol Commun. 2017 Jun 28;5(1):53.
[2]. Bailey DK, Clark W, Kosman DJ. The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells. PLoS One. 2021 Jul 26;16(7):e0254794.