Biological Activity
AER-271 is a phosphonate precursor (prodrug) form of the selective aquaporin 4 (AQP4) inhibitor IMD-0354 (AER-270; hu/m/r IC50 = 420/390/210 nM using respective CHO AQP4 transfectants) with >5000-fold enhanced solubility. AER-271 is rapidly converted to AER-270 in vivo (plasma AER-270 Cmax = 500 ng/mL or 1.75 μM, 20 min post 10 mg AER-271/kg i.p.; C57BL/6 mice) and exhibits therapeutic efficacy in rodent models of brain damage by cardiac arrest or ischemic stroke (5-10 mg/kg ip. & 0.08 mg/h sc. in mice; 1-10 mg/kg iv. in rats).
