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Christensen MB, Lund AB, Jrgensen NR, Holst JJ, Vilsbll T, Knop FK (2020) Glucose-dependent insulinotropic polypeptide (GIP) reduces bone resorption in patients with type 2 diabetes

doi: 10.1093/ndt/gfq818 105

Although several PPI inhibitors with improved selectivity have recently been identified, using combined approaches that brought together protein crystallography, ligand NMR spectroscopy, and computational chemistry, unfortunately, none of them has been found to be able to cross the BBB and many are quite large in size and contain carboxylic acids, features which usually prevent or decrease CNS permeability [299]

This small chemical change makes a big difference

amarum ) (Safitri et al., 2019)