Akt (Protein kinase B, PKB) family

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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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].

Enzymes

Targets of relevance to immunopharmacology are highlighted in blue

Akt1 (AKT serine/threonine kinase 1) Show summary »« Hide summary More detailed page

Akt2 (AKT serine/threonine kinase 2) Show summary »« Hide summary More detailed page

Target Id

1480

Nomenclature

AKT serine/threonine kinase 2

Common abbreviation

Akt2

Previous and unofficial names

Genes

AKT2 (Hs), Akt2 (Mm), Akt2 (Rn)

Ensembl ID

ENSG00000105221 (Hs), ENSMUSG00000004056 (Mm), ENSRNOG00000018677 (Rn)

UniProtKB AC

P31751 (Hs), Q60823 (Mm), P47197 (Rn)

EC number

2.7.11.11

Inhibitors

uprosertib pK_i 8.9 [4]

afuresertib pK_i 8.7 [4]

PHT-427 pK_i 5.6 [10]

GSK690693 pIC₅₀ 7.9 [5]

ipatasertib pIC₅₀ 7.7 [2]

Allosteric modulators

MK-2206 (Negative) pIC₅₀ 7.9 [12-13]

Akt inhibitor VIII (Negative) pIC₅₀ 6.7 [8]

AKT3 (AKT serine/threonine kinase 3) Show summary »« Hide summary More detailed page

References

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1. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P. (1997) Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr. Biol., 7 (4): 261-9. [PMID:9094314]

2. Blake JF, Xu R, Bencsik JR, Xiao D, Kallan NC, Schlachter S, Mitchell IS, Spencer KL, Banka AL, Wallace EM et al.. (2012) Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J. Med. Chem., 55 (18): 8110-27. [PMID:22934575]

3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

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]

5. Heerding DA, Rhodes N, Leber JD, Clark TJ, Keenan RM, Lafrance LV, Li M, Safonov IG, Takata DT, Venslavsky JW et al.. (2008) Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. J. Med. Chem., 51 (18): 5663-79. [PMID:18800763]

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]

11. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307 (5712): 1098-101. [PMID:15718470]

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.

How to cite this family page

Database page citation:

Akt (Protein kinase B, PKB) family. Accessed on 16/07/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=285.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Enzymes. Br J Pharmacol. 176 Issue S1: S297-S396.