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PPQ-102

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Chemical Structure| 931706-15-9 同义名 : CFTR Inhibitor;Cystic Fibrosis Transmembrane Conductance Regulator Inhibitor IV;CFTR Inhibitor IV
CAS号 : 931706-15-9
货号 : A621408
分子式 : C26H22N4O3
纯度 : 98%
分子量 : 438.478
MDL号 : MFCD14824240
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(114.03 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 CFTR is a chloride channel, that controls ion and water secretion and absorption in epithelial tissues. CFTR protein dysfunction leads to abnormal ion transport across the airway epithelium[3]. PPQ2 as a small molecule CFTR inhibitor that completely inhibited CFRR chloride current with IC50 value of 90 nM[4]. In vitro, PPQ-102 at the dose of 10µM inhibited CFTR almost 100% in (nonpermeabilized) human intestinal (T84) and bronchial cells following maximal CFTR activation by forskolin and IBMX. However, PPQ-102 did not inhibit calcium-activated chloride channels or cellular cAMP production[4]. PPQ-102 also inhibited the volume-regulated anion channel (VRAC) conductance with IC50 value of 20μM in HEK293 cells[5]. Treatment of NCI-H292 cells with 10μM PPQ-102 induced a two-fold increase in VEGF-A synthesis[3]. In the presence of NADPH, PPQ-102 lost in hepatic microsomes about 60% within 30min. No loss of PPQ-102 was seen in the absence of NADPH. In vivo, PPQ-102 was undetectable in serum, kidney and urine at 30-60 min after intravenous administration of 300μg PPQ-102 by LC/MS assay with sensitivity better than 100nM[6].
作用机制 PPQ-102 inhibits CFTR by an altered channel gating mechanism, with stabilization of the channel closed state[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.28mL

0.46mL

0.23mL

11.40mL

2.28mL

1.14mL

22.81mL

4.56mL

2.28mL
参考文献

[1]Martin C, Coolen N, et al. CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium. Eur Respir J. 2013 Dec;42(6):1553-62.

[2]Tradtrantip L, Sonawane ND,et al. Nanomolar potency pyrimido-pyrrolo-quinoxalinedione CFTR inhibitor reduces cyst size in a polycystic kidney disease model. J Med Chem. 2009 Oct 22;52(20):6447-55.

[3]Martin C, Coolen N, Wu Y, Thévenot G, Touqui L, Prulière-Escabasse V, Papon JF, Coste A, Escudier E, Dusser DJ, Fajac I, Burgel PR. CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium. Eur Respir J. 2013 Dec;42(6):1553-62

[4]Tradtrantip L, Sonawane ND, Namkung W, Verkman AS. Nanomolar potency pyrimido-pyrrolo-quinoxalinedione CFTR inhibitor reduces cyst size in a polycystic kidney disease model. J Med Chem. 2009 Oct 22;52(20):6447-55

[5] Friard J, Tauc M, Cougnon M, Compan V, Duranton C, Rubera I. Comparative Effects of Chloride Channel Inhibitors on LRRC8/VRAC-Mediated Chloride Conductance. Front Pharmacol. 2017 May 31;8:328

[6] Snyder DS, Tradtrantip L, Yao C, Kurth MJ, Verkman AS. Potent, metabolically stable benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR inhibitors for polycystic kidney disease. J Med Chem. 2011 Aug 11;54(15):5468-77