| References: |
Sodium-phosphate cotransporter 2a, or NaPi2a (SLC34A1), is a solute-carrier (SLC) transporter located in the kidney proximal tubule that reabsorbs glomerular-filtered phosphate. Inhibition of NaPi2a may enhance urinary phosphate excretion and correct maladaptive mineral and hormonal derangements associated with increased cardiovascular risk in chronic kidney disease–mineral and bone disorder (CKD-MBD).PF-06869206 is the first orally bioavailable selective NaPi2a inhibitor and, as such, represents a pharmacological tool to probe the functional effects of selective NaPi2a inhibition in vivo. PF-06869206 showed a balance of attributes with 380 nM NaPi2a inhibition potency, excellent subtype selectivity, and acceptable aqueous solubility (46 μM). Furthermore, permeability is good (14 × 10−6 cm/s), and RLM clearance is low (<14 μL/min/mg; HLM = 39 μL/min/mg). |
