PF-06869206

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Chemical Structure| 2227425-05-8 同义名 : -
CAS号 : 2227425-05-8
货号 : A393036
分子式 : C15H14ClF3N4O2
纯度 : 99%+
分子量 : 374.745
MDL号 : MFCD31657405
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(280.19 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.67mL

0.53mL

0.27mL

13.34mL

2.67mL

1.33mL

26.68mL

5.34mL

2.67mL
参考文献

[1]Wagner CA, Hernando N, Forster IC, Biber J. The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch. 2014;466(1):139‐153.

[2]Filipski KJ, Sammons MF, Bhattacharya SK, et al. Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1). ACS Med Chem Lett. 2018;9(5):440‐445.

[3]Thomas L, Xue J, Murali SK, Fenton RA, Dominguez Rieg JA, Rieg T. Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice with Normal and Reduced Kidney Function. J Am Soc Nephrol. 2019;30(11):2128‐2139.