[The cell permeable GGCT Inhibitor] Pro-GA [FDV-0019]_Funakoshi - 코아사이언스

For research of glutathione metabolic cycle

Pro-GA

The cell permeable GGCT Inhibitor

Cat.# FDV-0019 / Size: 2mg / Storage: -20℃

 

GGCT (γ-Glutamylcyclotransferase, C7orf24) is a glutathione homeostasis-related enzyme, which is highly

expressed in cancer cells. While GGCT ｅxpression is low in normal cells, GGCT overexpressed cells

dramatically increase its proliferation. Meanwhile, cell proliferation and migration are suppressed in GGCT

KO cancer cells. This knowledge suggests that GGCT accelerates cell proliferation.

Existing GGCT inhibitors, such as N-glutaryl-L-alanine (GA), do not have cell membrane permeability,

and cannot be used for cell culture and animal experiment.

Pro-GA is the world’s first pro-drug type of GA, which penetrates into cells with inhibition activity to GGCT.

This product has been commercialized with the support of Kyoto Pharmaceutical University. 

Features 

• Pro-drug type of N-glutaryl-L-alanine (GA)
• High cell membrane permeability 
• Transient inhibition of GGCT activity
• Specifically suppresses proliferation of cancer cells.
• Compatible to in vitro and in vivo use (not for human or veterinary use)  

 

Chemical Information 

• Molecular Formula: C12H19O7N  
• Chemical Structure: see below
• Molecular Weight: 289.28 
• Solubility: Soluble in DMSO

Conversion in cell and Application Data of Pro-GA 

 

Fig.1 GA-release efficiency of Pro-GA in cells
MCF7 cells were treated with 100 μM of fluorescent NBD-conjugated Pro-GA for 0-60 min. After washing, cell lysates were prepared and analyzed by HPLC to evaluate GA amount released from Pro-GA. NBD-conjugated Pro-GA was immediately incorporated into cells within a few minutes and converted to GA in the cells.

Fig.2 Inhibition of proliferation in cancer cells
Cells were cultured in serum starve condition with DMSO (as control), GA or Pro-GA for the indicated days. Cell proliferation was measured by WST cell viability assay. Pro-GA specifically suppressed proliferation of cancer cells.

Fig.3 Stability of Pro-GA in culture medium at room temperature

Stabilities of fluorescent NBD-conjugated Pro-GA in PBS or 10% FBS/DMEM were tested by HPLC analysis. While conversion of Pro-GA to GA was slowly in PBS (t1/2>5 hours), Pro-GA was quickly converted into GA in 10% FBS/DMEM by esterase activity in FBS (t1/2~50 min). 

Please prepare Pro-GA solution in assay medium just before use.

References 

1. Oakley et al., J. Biol. Chem. 283, 22031-22042, (2008) 

2. Kageyama et al., Proteomics Clin. Appl., 1, 192-199 (2007) 

3. Ii et al., ChemMedChem., 13, 155-163 (2018)

 

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