Aleplasinin

Aleplastinin (PAZ-417) is an orally active, blood-brain barrier permeable, selective SERPINE1 (PAI-1) inhibitor (IC₅₀=655 nM). Aleplastinin activates the tissue type plasminogen activator (tPA)/fibrinolysis cascade by inhibiting PAI-1, thereby promoting the degradation of amyloid-β (Aβ) oligomers and monomers. Aleplastinin can significantly reduce plasma and brain Aβ levels, improve memory impairment, and reverse cognitive impairment. Aleplastinin can be used for research on Alzheimer's disease^[1][2]. In Vitro:Aleplasinin (5 μM) restores PAI-1-inhibited cleavage of monomeric and oligomeric Aβ₄₂ by 93% in vitro using recombinant human PAI-1, purified tPA, and plasminogen^[1]. In Vivo:Aleplastinin (20 mg/kg, p.o., single dose) reduces plasma Aβ₄₀and brain Aβ_40/42in Tg2576 transgenic mice (Alzheimer's disease model), while 30-100 mg/kg (p.o.) reverses the long-term potentiation (LTP) deficiency in the hippocampus of Tg2576/PSAPP mice and improve situational memory impairment^[1].