ARN1468 (compound 5) is an orally active and potent serpins inhibitor. ARN1468 can inhibit serpins activity would set the protease free to further reduce prion accumulation. ARN1468 shows anti-prion effect in ScGT1 RML, ScGT1 22L, ScN2a RML, and ScN2a 22L cell lines, with EC50 values of 8.64, 19.3, 11.2, and 6.27 μM[1].
ARN1468 (compound 5) (3 mg/kg, IV; 10 mg/kg, PO; once) reveals low brain concentrations and high plasma clearance in male C57BL/6 mice[1].
[1]. Colini Baldeschi A, et al. Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance. J Med Chem. 2022 Jun 30.