GlyH-101

GlyH-101 Property

Melting point:

>300℃ (ethanol )

Density 

1.73±0.1 g/cm3(Predicted)

storage temp. 

= -70C

solubility 

DMF:30.0(Max Conc. mg/mL);60.83(Max Conc. mM)
DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.01(Max Conc. mM)
DMSO:57.58(Max Conc. mg/mL);116.75(Max Conc. mM)

form 

Yellow solid

pka

5.44±0.45(Predicted)

color 

Light yellow to yellow

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

GlyH-101 Chemical Properties,Usage,Production

Description

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.

Uses

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.

Definition

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

General Description

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.

Biochem/physiol Actions

Cell permeable: yes

storage

Store at -20°C

References

[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
[4] L J MACVINISH. Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR.[J]. British Journal of Pharmacology, 2007, 150 8: 1055-1065. DOI: 10.1038/sj.bjp.0707175
[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