| Description | 6-Aminonicotinamide (6AN) is an antimetabolite used to inhibit the NADPH-producing pentose phosphate pathway (PPP) in many cellular systems, making them more susceptible to oxidative stress. 6-Aminonicotinamide is a competitive inhibitor of NADP+-dependent enzyme glucose-6-phosphate dehydrogenase (G6PD) with Ki of 0.46 μM. | ||
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| In vitro | Blocking the pentose phosphate pathway (PPP) by 6-AN significantly inhibits mES colony formation in the presence of a normal concentration of glucose. 6-AN treatment effectively inhibits AKT phosphorylation and activation of its downstream effector S6. 6-AN treatment has no effect on the ERK and PDK1 activities, suggesting an AKT-specific effect. 6-AN treatment inhibits cell growth.[2] | ||
| In vivo | PTEN null human cancer cells and in vivo murine models are sensitive to 6-AN (anti-PPP, anti pentose phosphate pathway) treatments, suggesting the importance of the PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. The treatment of TALL models with 6-AN significantly increases the Phlda3 mRNA and protein levels, accompanied by substantial decreases in the levels of P-AKT and P-S6 as well as the PPP metabolic intermediates.[2] |
