GGsTop 926281-37-0 GlpBio

Peptides, Inhibitors, Agonists
Product Data Sheet
Product Name: GGsTop
Cat. No.:GC16612
Chemical Name: (S)-2-amino-4-((S)-(3-(carboxymethyl)phenoxy)(methoxy)phosphoryl)butanoic acid
CHEMICAL PROPERTIES
Cas No.: 926281-37-0
Molecular Formula: C13H18NO7P
Molecular Weight: 331.26
Storage: Powder
Solubility: Soluble in DMSO
Chemical Structure:
Background
GGsTop is a novel is a novel, highly selective, and irreversible γ-glutamyl transpeptidase (GGT) inhibitor with Ki of 0.17 mM. [1]
GGT plays an important role in the metabolism of plasma glutathione (GSH) and its S-conjugates via the cleavage of the γ-glutamyl amide bond by hydrolysis and/or transpeptidation. GGT exists in the lung as a soluble enzyme in association with surfactant phospholipids and controls turnover of the extracellular pool of glutathione in LLF (lung lining uid). In the human enzyme, a specific residue in the Cys - Gly binding site played a critical role in recognizing the Cys - Gly moiety or the acceptor molecules by interacting with the C-terminal carboxy group, whereas the Cys side chain and the Cys - Gly amide bond were not recognized significantly. GGsTop was found for its potency against GGT in a series of analogues designed for structure-activity relationships. [1, 2]
The inactivation rates of E. coli and human GGT by GGsTop were studied. GGsTop showed a good potency against GGT in both species. Furthermore, the kinetics of GGsTop for human GGT was also measured and its Ki value is 0.17 mM. [1]
In the IL-13 model, mice treated with IL-13 and GGsTop exhibit a lung in ammatory response similar to that of mice administrated with IL-13 alone. However, mice treated with IL-13 and GGsTop exhibit attenuation of methacholine-stimulated airway hyper-reactivity, inhibitory effect of Muc5ac and Muc5b gene induction, decreased epithelial cell mucous accumulation in the airway and a 4-fold increase in LLF glutathione content compared to mice in IL-13 group. The associated increase in LLF glutathione can protect lung airway epithelial cells against oxidant injury associated with in ammation in asthma. Moreover, ischemic acute kidney injury (AKI) was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion 2 weeks after contralateral nephrectomy. Renal
function in control significantly decreased at 1 day after reperfusion. Rats administrated with GGsTop at doses of 1 and 10 mg per kg i.v. 5 min before ischemia attenuated the I/R-induced renal dysfunction in a dose-dependent manner. Histopathological evaluation of the kidney of AKI rats revealed severe renal damages, whereas they were significantly suppressed by the GGsTop treatment. [2, 3]
References:
[1]Ndubaku CO1, Heffron TP, Staben ST, Baumgardner M, Blaquiere N, Bradley E, Bull R, Do S, Dotson J, Dudley D, Edgar KA, Friedman LS, Goldsmith R, Heald RA, Kolesnikov A, Lee L, Lewis C, Nannini M, Nonomiya J, Pang J, Price S, Prior WW, Salphati L, Sideris S, Wallin JJ, Wang L, Wei B, Sampath D, Olivero AG. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013 Jun 13;56(11):4597-610.
Research Update
1. Effect of Hydrofluoric Acid Concentration and Etching Time on Bond Strength to Lithium Disilicate Glass Ceramic. Oper Dent. 2017 Nov/Dec;42(6):606-615. doi: 10.2341/16-215-L. Epub 2017 Jul 14. PMID:28708007
Abstract
The aim of this study was to evaluate the influence of different concentrations of hydrofluoric acid (HF) associated with varied etching times on the microshear bond strength (μSBS) of a resin cement to a lithium disilic ate glass ceramic. Two hundred seventy-five ceramic blocks (IPS e.max Press [EMX], Ivoclar Vivadent), measuring 8 mm × 3 mm thickness, were randomly distributed into fiv e groups according to the HF concentrations (n=50): 1%, 2.5%, 5%, 7.5%, and 10%.
2. Does acid etching morphologically and chemically affect lithium disilicate glass ceramic surfaces? J Appl Biomater Funct Mater. 2017 Jan 26;15(1):e93-e100. doi: 10.5301/jabfm.500030
3. PMID:27647389
Abstract
BACKGROUND: This study evaluated the surface morphology, chemical composition and adhesiveness of lithium disilicate glass ceramic after acid etching with hydrofluoric acid or phosphoric acid.METHODS: Lithium disilicate glass ceramic specimens polished by 600-grit silicon carbide paper were subjected to one or a combination of these surface treatments: airborne particle abrasion with 50-μm alumina (AA), etching with 5% hydrofluoric acid (HF) or 36% phosphoric acid (Phos), and application of silane coupling age nt (Si).
3. Fatigue failure load of feldspathic ceramic crowns after hydrofluoric acid etching at different concentrations. J Prosthet Dent. 2018 Feb;119(2):278-285. doi: 10.1016/j.prosdent.2017.03.021. Epub 2017 May 26. PMID:28552291
Abstract
STATEMENT OF PROBLEM: Hydrofluoric acid etching modifies the cementation surface of ceramic restorations, which is the same surface where failure is initiated. Information regarding the influence of hydrofluoric acid etching on the cyclic loads to failure of ceramic crowns is lacking.PURPOSE: The purpose of this in vitro study was to evaluate the influence of different hydrofluoric acid concentrations on the fatigue failure loads of feldspathic ceramic crowns.。