ipsu

Description: IPSU is a novel, potent, selective, orally bioavailable and brain penetrant OX2R antagonist with a pKi of 7.85. IPSU binds rapidly and reaches equilibrium very quickly in binding and/or functional assays. Overall, IPSU tends to be rather unselective under non-equilibrium conditions and reaches equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the 'dual' antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo.

References: Front Neurosci. 2013 Dec 3; 7:230; J Med Chem. 2013 Oct 10; 56(19):7590-607.