The action of phosphatidylinositol 3-kinase (PI3K), a downstream kinase activated by receptor tyrosine kinases, produces a series of phosphorylated phosphoinositides, which recruit 3-phosphoinositide-dependent kinase (PDPK1, O15530) activity to the plasma membrane, leading to activation of Akt. Akt may be activated by PIP₃, PDK1-mediated phosphorylation [1] and mTORC2-mediated phosphorylation [6,11].

* Key recommended reading is highlighted with an asterisk

* Lazaro G, Kostaras E, Vivanco I. (2020) Inhibitors in AKTion: ATP-competitive vs allosteric. Biochem Soc Trans, 48 (3): 933-943. [PMID:32453400]

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4. Dumble M, Crouthamel MC, Zhang SY, Schaber M, Levy D, Robell K, Liu Q, Figueroa DJ, Minthorn EA, Seefeld MA et al.. (2014) Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS ONE, 9 (6): e100880. [PMID:24978597]

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6. Hresko RC, Mueckler M. (2005) mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. J Biol Chem, 280 (49): 40406-16. [PMID:16221682]

7. Lin H, Yamashita DS, Zeng J, Xie R, Verma S, Luengo JI, Rhodes N, Zhang S, Robell KA, Choudhry AE et al.. (2010) 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett, 20 (2): 679-83. [PMID:20005102]

8. Lindsley CW, Zhao Z, Leister WH, Robinson RG, Barnett SF, Defeo-Jones D, Jones RE, Hartman GD, Huff JR, Huber HE et al.. (2005) Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett, 15 (3): 761-4. [PMID:15664853]

9. Luo Y, Shoemaker AR, Liu X, Woods KW, Thomas SA, de Jong R, Han EK, Li T, Stoll VS, Powlas JA et al.. (2005) Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol Cancer Ther, 4 (6): 977-86. [PMID:15956255]

10. Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R et al.. (2010) Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther, 9 (3): 706-17. [PMID:20197390]

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12. Yan L. Abstract #DDT01-1: MK-2206: A potent oral allosteric AKT inhibitor. Accessed on 18/11/2014. Modified on 18/11/2014. AACR Meeting Abstracts Online; http://aacrmeetingabstracts.org, http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2009/2_Annual_Meeting/DDT01-1?maxtoshow=&hits=10&RESULTFORMAT=1&title=MK-2206&andorexacttitle=and&andorexacttitleabs=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2008&tdate=12/31/2010&resourcetype=HWCIT

13. Yan L. (2009) MK-2206: a potent oral allosteric AKT inhibitor.[Abstract]. AACR Annual Meeting 2009,: Abstract Number: DDT01-1.