Phosphate is an essential mineral component of bone, membranes, nucleic acids, nucleotides, and second messengers and is key to cellular processes involving kinases and phosphatases[1]. The three members of the NaPi2 family of solute carrier (SLC) sodium-phosphate cotransporters, NaPi2a (SLC34A1) NaPi2c (SLC34A3) and NaPi2b (SLC34A2) play an important role in phosphate homeostasis. PF-06869206 is an orally bioavailable selective inhibitor of the sodium-phosphate cotransporter NaPi2a (SLC34A1) with an IC50 of 380 nM[2]. In normal mice, PF-06869206 dose-dependently increased urinary phosphate with ED50 approximately 21 mg/kg, calcium, sodium and chloride excretion, without effects on urinary potassium excretion, flow rate and urinary pH. Three hours after PF-06869206 (30 mg/kg p.o.) treatment, plasma phosphate and parathyroid hormone significantly decreased, with both returning to near baseline levels after 24 hours, which were also observed in the mouse model of CKD (Chronic kidney disease) but were reduced in magnitude[3].
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