PF-06869206

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-06869206 是钠-磷酸盐协同转运蛋白 NaPi2a 的口服选择性抑制剂（SLC34A1，IC50：380 nM）。

PF-06869206 is an oral selective inhibitor of the sodium-phosphate cotransporter NaPi2a (SLC34A1, IC50: 380 nM).

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.

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), andrat liver microsome (RLM) clearance is low (<14 μL/min/mg; HLM=39 μL/min/mg).

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Membrane Transporter/Ion Channel

Sodium Channel

SLC34A1

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2227425-05-8

374.75

C15H14ClF3N4O2

>98% (HPLC)

DMSO:120 mg/mL (320.22 mM)

CC1=C(C2=C(N1)C(=C(C(=N2)C(F)(F)F)C#N)N3CCO[C@@H](C3)CO)Cl

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(-20℃)

With Ice Pack

≥ 2 years