PF-06869206

PF-06869206 is an orally bioavailable selective inhibitor of the sodium-phosphate cotransporter NaPi2a (SLC34A1) with an IC50 of 380 nM.

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Metabolic Disease

IC50: 380 nM (NaPi2a/SLC34A1)[1]

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 IC50s of 0.4±0.047 μM and 0.54±0.099 μM for rat NaPi2a and mouse NaPi2a, respectively[1].

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 (t1/2=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)[1].

Rats and Mice[1] Male Wistar-Han rats (n=2) are treated with PF-06869206 (1 mg/kg, 5 mg/kg, and 50 mg/kg; 2 mL/kg for iv or 10 mL/kg for po) . C57BL6 mice (n=2) are treated with PF-06869206 (1 mg/kg, 5 mg/kg, and 50 mg/kg; 2 mL/kg for iv or 10 mL/kg for po) [1].

[1]. Filipski KJ, et al. Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1). ACS Med Chem Lett. 2018 Apr 12;9(5):440-445.

EIPA | Riluzole | Ginsenoside Rg3 | Cariporide | Eleclazine hydrochloride | GS967 | Tenapanor | Triamterene | Ranolazine dihydrochloride | PF 05089771 | flecainide acetate | A-803467 | CNV1014802 (hydrochloride) | Zonisamide | Cinchocaine