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).
Phosphonate precursor (prodrug) of the selective aquaporin 4 (AQP4) inhibitor IMD-0354 (AER-270) with in vivo efficacy in rodent models of brain damage.
Aquaporins (AQPs) are water channels that mediate a variety of biological processes. However, their role in the immune system is poorly understood. We recently reported that AQP4 is expressed by naïve and memory T cells and that AQP4 blockade with
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 18(5), 1238-1246 (2017-12-16)
Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal allografts and expand
Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema
Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA
