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Final compound dilution occurs post-injection giving a final concentration of 50, 35, 25, 12.5, 10 and 5 M inside the well

The mode of therapeutic action of NAC is believed to involve its hydrolysis in the affected cells to cysteine, leading to increased synthesis of GSH

Wong et al., 2021)

The universal role of NADPH as the primary electron donor for most biological reductions, including for supporting disulfide reduction systems, made the uncovering of an apparently NADPH-independent disulfide reduction system in mouse liver surprising

TGR inhibitors do not react covalently with GSH, selenocysteine, or TGR, and inhibition of TGR is reversible To evaluate stability of the TGR inhibitors in the presence of GSH and selenocysteine, compound 2 and a known covalent inhibitor of TGR, TRi-1 20,45 , were incubated with GSH or the N-Boc protected methyl ester of selenocysteine, and the reaction mixtures were analyzed by LCMS (Supplementary Figs