pbt 434

U 80215 is an enzyme-competitive inhibitor.

PBT434 is a novel, brain-penetrant, small molecule inhibitor of α-synuclein aggregation. In transgenic animal models of Parkinson disease (A53T) and MSA (PLP-α-Syn), PBT434 reduced α-synuclein aggregation, preserved neurons and improved motor function. Glial cell inclusions were also reduced in a murine MSA model. PBT434 is thought to act by redistributing reactive iron across membranes, thereby blocking intracellular protein aggregation and oxidative stress. The affinity of PBT434 for iron is greater than that of α-synuclein but lower than that of iron trafficking proteins, e.g., ferritin.

PBT434 methanesulfonate 为一种有效、口服活性并能穿透血脑屏障的α-synuclein aggregation抑制剂，同时担任铁螯合剂和跨细胞铁运输的调节剂。该化合物抑制铁介导的氧化还原活性及α-synuclein聚集，可有效防止SNpc神经元丢失，显示出在PD研究中的应用潜力。