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| | PF06869206 Basic information | | In Vivo |
| Product Name: | PF06869206 | | Synonyms: | PF06869206;PF-06869206;CS-2762;PF-06869206; PF 06869206; PF06869206;1H-Pyrrolo[3,2-b]pyridine-6-carbonitrile, 3-chloro-7-[(2S)-2-(hydroxymethyl)-4-morpholinyl]-2-methyl-5-(trifluoromethyl)-;(S)-3-Chloro-7-(2-(hydroxymethyl)morpholino)-2-methyl-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile;inhibit,PF-06869206,Na+ channels,Sodium Channel,Na channels,PF 06869206,Inhibitor,PF06869206 | | CAS: | 2227425-05-8 | | MF: | C15H14ClF3N4O2 | | MW: | 374.75 | | EINECS: | 604-604-1 | | Product Categories: | | | Mol File: | 2227425-05-8.mol |  |
| | PF06869206 Chemical Properties |
| Boiling point | 599.2±50.0 °C(Predicted) | | density | 1.57±0.1 g/cm3(Predicted) | | storage temp. | 2-8°C | | solubility | DMF: 1 mg/mL; DMSO: 1mg/mL; Ethanol: 10mg/mL; Ethanol:PBS (pH 7.2) (1:3): 0.25 mg/mL | | form | A crystalline solid | | pka | 11.78±0.40(Predicted) |
| | PF06869206 Usage And Synthesis |
| In Vivo | 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). | | Description | PF-06869206 is an orally bioavailable inhibitor of sodium-phosphate cotransporter 2a (NaPi2a; IC50 = 380 nM). It is selective for NaPi2a over NaPi2b, NaPi2c, PiT-1, and PiT-2 (IC50s = >25 μM). | | Biological Activity | PF-06869206 (PF06869206) is a potent, selective, orally bioavailable inhibitor of sodium-phosphate cotransporter 2a (NaPi2a/SLC34A1) with IC50 of 380 nM, no inhibition against NaPi2b (SLC34A2) and NaPi2c (SLC34A3).PF-06869206 displays excellent subtype selectivity against other sodium-phosphate cotransporters: NaPi2b, NaPi2c, PiT-1, and PiT-2 (SLC20A2).PF-06869206 showed comparable submicromolar activity for the human, rat, and mouse NaPi2a isoforms (IC50=0.4-0.54 uM) and was selective over rodent NaPi2c, inhibited phosphate uptake in human proximal tubule cells.PF-06869206 was well tolerated and elicited a dose-dependent increase in fractional phosphate excretion, lowered plasma phosphate levels in WT mice and in rats with chronic kidney disease (CKD), induced an unabated acute phosphaturic and hypophosphatemic effect in CKD rats. | | in vitro | 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. |
| | PF06869206 Preparation Products And Raw materials |
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