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. Author manuscript; available in PMC: 2010 May 1.
Published in final edited form as: Cell Signal. 2009 Jan 7;21(5):656–664. doi: 10.1016/j.cellsig.2009.01.004

Figure 3. Pharmaceutical approaches to inhibit the mTOR pathway via AMPK.

Figure 3

Because AMPK inhibits mTORC1 by direct and indirect mechanisms, drugs that activate AMPK could be effective in the treatment of cancer. The best-described AMPK activators (shown in bold) are metformin, AICAR, 2-DG, PIAs, and A-769662. Metformin is a biguanide widely prescribed for the treatment of type II diabetes, AICAR is an AMP mimetic, and 2-DG is a glucose analogue. These three drugs activate AMPK by mechanisms that are dependent upon the upstream kinase and tumor suppressor, LKB1. Conversely, the lipid-based Akt inhibitors, PIAs, activate AMPK independently of LKB1 (or Akt, not shown). However, cellular activation of AMPK by PIAs is dependent upon another upstream kinase, CaMKKβ. The thienepyridone A-769662 activates purified AMPK in vitro, and might also activate AMPK directly in cells.