CFTR Inhibitor II(GlyH101)

CFTR Inhibitor II is a CFTR inhibitor (cystic fibrosis transmembrane conductance regulator). CFTR Inhibitor II is a glycine hydrazide that has been shown to block CFTR channels. CFTR Inhibitor II blocked I(Cl.PKA) in a concentration- and voltage-dependent fashion (IC(50) at +100 mV=0.3 ± 1.5 μM and at -100 mV=5.1 ± 1.3 μM). CFTR Inhibitor II blocks the open pore of cardiac CFTR channels at an electrical distance of 0.15 ± 0.03 from the external membrane surface.

Product information

CAS Number: 328541-79-3

Molecular Weight: 493.15

Formula: C19H15Br2N3O3

Synonym:

GlyH-101

GlyH 101

GlyH101

Chemical Name:  (E)-N'-(3,5-dibromo-2,4-dihydroxybenzylidene)-2-(naphthalen-2-ylamino)acetohydrazide

Smiles: OC1=C(/C=N/NC(=O)CNC2=CC=C3C=CC=CC3=C2)C=C(Br)C(O)=C1Br

InChiKey: RMBDLOATEPYBSI-NUGSKGIGSA-N

InChi: InChI=1S/C19H15Br2N3O3/c20-15-8-13(18(26)17(21)19(15)27)9-23-24-16(25)10-22-14-6-5-11-3-1-2-4-12(11)7-14/h1-9,22,26-27H,10H2,(H,24,25)/b23-9+

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

CFTR Inhibitor II reversibly inhibits CFTR Cl- conductance in <1 min. In rabbit isolated ventricular myocytes, CFTR Inhibitor II also blocks cardiac I(Cl.PKA) channels. In transfected FRT (SLC26A9-FRT) cells, CFTR Inhibitor II inhibits SLC26A9-mediated Cl- currents.

In Vivo:

In mice, Topical CFTR Inhibitor II (10 μM) in mice rapidly and reversibly inhibits forskolin-induced hyperpolarization in nasal potential differences. In a cholera model, intraluminal CFTR Inhibitor II (2.5 μg) reduces cholera toxin-induced intestinal fluid secretion by approximately 80%.

References:

1. Melis N, Tauc M, Cougnon M, Bendahhou S, Giuliano S, Rubera I, Duranton C. Revisiting CFTR inhibition: a comparative study of CFTRinh -172 and GlyH-101 inhibitors. Br J Pharmacol. 2014 Aug;171(15):3716-27. doi: 10.1111/bph.12726. PubMed PMID: 24758416; PubMed Central PMCID: PMC4128068.
2. Norimatsu Y, Ivetac A, Alexander C, O'Donnell N, Frye L, Sansom MS, Dawson DC. Locating a plausible binding site for an open-channel blocker, GlyH-101, in the pore of the cystic fibrosis transmembrane conductance regulator. Mol Pharmacol. 2012 Dec;82(6):1042-55. doi: 10.1124/mol.112.080267. Epub 2012 Aug 24. PubMed PMID: 22923500; PubMed Central PMCID: PMC3502623.
3. Sheppard DN. CFTR channel pharmacology: insight from a flock of clones. Focus on "Divergent CFTR orthologs respond differently to the channel inhibitors CFTRinh-172, glibenclamide, and GlyH-101". Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C24-6. doi: 10.1152/ajpcell.00376.2011. Epub 2011 Oct 12. PubMed PMID: 21998142.
4. Stahl M, Stahl K, Brubacher MB, Forrest JN Jr. Divergent CFTR orthologs respond differently to the channel inhibitors CFTRinh-172, glibenclamide, and GlyH-101. Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C67-76. doi: 10.1152/ajpcell.00225.2011. Epub 2011 Sep 21. PubMed PMID: 21940661; PubMed Central PMCID: PMC3328903.
5. Barman PP, Choisy SC, Gadeberg HC, Hancox JC, James AF. Cardiac ion channel current modulation by the CFTR inhibitor GlyH-101. Biochem Biophys Res Commun. 2011 Apr 29;408(1):12-7. doi: 10.1016/j.bbrc.2011.03.089. Epub 2011 Mar 31. PubMed PMID: 21439936.

Products are for research use only. Not for human use.