G6PD activator AG1

• CAT Number: I018729
• CAS Number: 421581-52-4
• Molecular Formula: C24H30N4S2
• Molecular Weight: 438.65
• Purity: ≥95%
• Synonyms: 2-(1H-indol-3-yl)-N-[2-[2-[2-(1H-indol-3-yl)ethylamino]ethyldisulfanyl]ethyl]ethanamine
• InChI: InChI=1S/C24H30N4S2/c1-3-7-23-21(5-1)19(17-27-23)9-11-25-13-15-29-30-16-14-26-12-10-20-18-28-24-8-4-2-6-22(20)24/h1-8,17-18,25-28H,9-16H2
• InChIKey: AJBHTYKMNQDUAA-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C(=CN2)CCNCCSSCCNCCC3=CNC4=CC=CC=C43

G6PD activator AG1 is a potent and selective glucose-6-phosphate dehydrogenase (G6PD) activator with an EC50 of 3 µΜ[1]. G6PD activator AG1 reduces hemolysis of human erythrocytes[2].
AG1 (50, 100, 250, 500, 750, 1000 nM) of 1?μM increases the viability by 20% and the proteolytic stability of Canton G6PD in SH-SY5Y cells. AG1 has no effect when G6PD was knocked down by siRNA, supporting the specificity of AG1 toward G6PD[2].
AG1 (1-5 μΜ; pre-incubated overnight) reduces the extent of hemolysis with 5 μΜ in human erythrocytes suspension (5%) exposed to either 1 mM chloroquine (CQ; 4 hours) or diamide (a GSH oxidant; 4 hours). AG1 increases GSH levels and reduced ROS levels together with increased G6PD activity under these drug-induced oxidative stress[2].
AG1 has no effect on the dimerization or activity of several other NAD- or NADP+-dependent dimeric or tetrameric enzymes, including 6-phosphogluconate dehydrogenase (6PGD), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), aldehyde dehydrogenase 2 (ALDH2), and aldehyde dehydrogenase 3A1 (ALDH3A1)[2].

Reference

[1]. https://patents.google.com/patent/WO2019023264A1/en?oq=WO2019023264A1

[2]. Kaitlyn Ryan, et al. Current investigations on clinical pharmacology and therapeutics of Glucose-6-phosphate dehydrogenase deficiency. Pharmacol Ther. 2020 Dec 14;222:107788.
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