IC50: 380 nM (NaPi2a/SLC34A1)

PF-06869206 shows a balance of attributes with 380 nM NaPi2a inhibition potency, excellent subtype selectivity, and acceptable aqueous solubility (46 μM). PF-06869206 is profiled for potency in the rodent NaPi2a and NaPi2c cell lines. PF-06869206 shows comparable submicromolar activity for the human, rat, and mouse NaPi2a isoforms with IC ₅₀ s of 0.4±0.047 μM and 0.54±0.099 μM for rat NaPi2a and mouse NaPi2a, respectively.

PF-06869206 is evaluated in rodent PK studies to determine suitability for in vivo pharmacology exploration. Results show moderate clearance in both rat and mouse. Oral bioavailability at 5 mg/kg is good in rat and moderate in mouse. At higher oral doses of 50 mg/kg, supraproportional increases in exposure are observed in both species, suggestive of saturation of clearance. PF-06869206 has moderate terminal elimination half-life (t _1/2 =1.35 h, and 0.75 h for Wistar-Han rats (10 mg/kg, iv), and C57BL6 mice (1 mg/kg, iv)). Furthermore, permeability is good (14×10 ^-6 cm/s), and rat liver microsome (RLM) clearance is low (<14 μL/min/mg; HLM=39 μL/min/mg).