328541-79-3

The cystic fibrosis (CF) gene encodes a cAMP-regulated chloride channel, the CF transmembrane conductance regulator (CFTR). CFTR inhibitor II, also known as GlyH-101, is a glycine hydrazide that selectively and reversibly blocks the CFTR channel (K_i = 4.3 μM). This compound binds to a site at the external pore of CFTR, occluding the pore and rapidly preventing chloride transport. Intraluminal CFTR inhibitor II greatly reduces intestinal fluid secretion induced by cholera toxin. It is effective in cells in culture and also in nasal and intestinal epithelia in vivo.

N-2-Naphthalenyl-glycine 2-[(3,5-dibromo-2,4-dihydroxyphenyl)methylene]hydrazide is a glycine hydrazide that has recently been shown to block CFTR channels. However, its effects on cardiomyocytes are unknown. Studies have demonstrated that GlyH-101 blocks cardiac I Cl.PKA channels in a similar fashion to that reported for recombinant CFTR.

N-2-Naphthalenyl-glycine 2-[(3,5-dibromo-2,4-dihydroxyphenyl)methylene]hydrazide is a glycine hydrazide that has recently been shown to block CFTR channels. However, its effects on cardiomyocytes are unknown. Studies have demonstrated that GlyH-101 blocks cardiac I Cl.PKA channels in a similar fashion to that reported for recombinant CFTR.

ChEBI: Glycine, n-2-naphthalenyl-, 2-[(3,5-dibromo-2,4-dihydroxyphenyl)methylene]hydrazide is a member of naphthalenes.

A cell-permeable glycinyl hydrazone compound that acts as a potent, selective and reversible open-channel blocker of CFTR with intermediate speed (<1 min; 95% inhibition at 50 μM; K_i = 4.3 μM in CFTR-expressing FRT cells for apical membrane Cl^- current) and exhibits desirable aqueous solubility. Shown to produce inwardly rectifying CFTR Cl^- currents with reduced mean channel open time and suggested to directly interact with the channel pore at the extracellular side of the membrane. Displays minimal effects on P-glycoprotein and non-CFTR-mediated Cl^- currents, and is effective in nasal and intestinal epithelia in vivo.

Cell permeable: yes

Store at -20°C

[1] R. DE?RAND F B L Bulteau Pignoux. The Cystic Fibrosis Mutation G551D Alters the Non-Michaelis-Menten Behavior of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel and Abolishes the Inhibitory Genistein Binding Site*[J]. The Journal of Biological Chemistry, 2002, 12 1: 35999-36004. DOI: 10.1074/jbc.m206121200
[2] N. D. SONAWANE. Luminally active, nonabsorbable CFTR inhibitors as potential therapy to reduce intestinal fluid loss in cholera[J]. FASEB Journal, 2005, 20 1: 130-132. DOI: 10.1096/fj.05-4818fje
[3] CHATCHAI MUANPRASAT. Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy.[J]. Journal of General Physiology, 2004, 124 2: 125-137. DOI: 10.1085/jgp.200409059
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[5] JAMES P GARNETT. Protein phosphatase 1 coordinates CFTR-dependent airway epithelial HCO3? secretion by reciprocal regulation of apical and basolateral membrane Cl?-HCO3? exchangers[J]. British Journal of Pharmacology, 2012, 168 8: 1946-1960. DOI: 10.1111/bph.12085
[6] ERIC S SCHIFFHAUER. Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.[J]. American journal of physiology. Lung cellular and molecular physiology, 2013, 304 5: L324-31. DOI: 10.1152/ajplung.00277.2012
[7] S ZERTAL-ZIDANI. Small-molecule inhibitors of the cystic fibrosis transmembrane conductance regulator increase pancreatic endocrine cell development in rat and mouse.[J]. Diabetologia, 2013, 56 2: 330-339. DOI: 10.1007/s00125-012-2778-8