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NEWS ｜ 14 June 2024
WIKIMOLE—3-Methyladenine
By TargetMol
3-Methyladenine (Catalog No. T1879), also known as 3-MA, 3-Methyladenine, and NSC 66389, is a PI3K inhibitor that exerts its autophagy-inhibiting effects by inhibiting PI3K. It plays an important role in the study of cell signaling and autophagy processes.
Mechanism of Action
3-MA inhibits autophagy by blocking the formation of autophagosomes through the inhibition of class III PI3K complexes, playing a dual role in autophagy regulation. Long-term treatment with 3-MA can promote autophagy under nutrient-rich conditions, while it inhibits autophagy under starvation-induced conditions. This is attributed to 3-MA's differential effects on type I and type III PI3K; 3-MA's inhibition of type I PI3K is persistent, whereas its inhibitory effect on type III PI3K is transient.
Application
3-MA is an important tool compound widely used in the study of autophagy, signal transduction, and various aspects of cell biology. For example, as a PI3K inhibitor, 3-MA can be used to study the functions and regulation of the PI3K/Akt/mTOR signaling pathway, thereby enhancing our understanding of the roles these pathways play in cell growth, proliferation, and metabolism. On the other hand, because autophagy plays a crucial role in the survival and drug resistance of tumor cells, 3-MA is often used to investigate the effects of autophagy inhibition on tumor cells, exploring potential anticancer therapeutic strategies.
References
[1] Cheong H, Lu C, Lindsten T, Thompson CB. Therapeutic targets in cancer cell metabolism and autophagy. Nat Biotechnol. 2012;30(7):671-678. Published 2012 Jul 10. doi:10.1038/nbt.2285
[2] Wu Y. et al., 2010. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem. 285(14):10850-61.
[3] Ito S, Koshikawa N, Mochizuki S, Takenaga K. 3-Methyladenine suppresses cell migration and invasion of HT1080 fibrosarcoma cells through inhibiting phosphoinositide 3-kinases independently of autophagy inhibition. Int J Oncol. 2007;31(2):261-268.
[4] Hou H, Zhang Y, Huang Y, et al. Inhibitors of phosphatidylinositol 3'-kinases promote mitotic cell death in HeLa cells. PLoS One. 2012;7(4):e35665. doi:10.1371/journal.pone.0035665
[5] Seglen PO, Gordon PB. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci U S A. 1982;79(6):1889-1892. doi:10.1073/pnas.79.6.1889
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