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Akt Protein Kinase B

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Akt Inhibitors (14)

water-soluble

Cat.No. Product Name Information Product Citations Customer Reviews
S1078 MK-2206 2HCl MK-2206 2HCl is a highly selective inhibitor of Akt1, Akt2 and Akt3 with IC50 of 8 nM, 12 nM and 65 nM, respectively.
S1037 Perifosine Perifosine (KRX-0401) is a novel Akt inhibitor with IC50 of 4.7 μM.
S1113 GSK690693 GSK690693 is a pan-Akt inhibitor targeting Akt1, Akt2 and Akt3 with IC50 of 2 nM, 13 nM, and 9 nM, respectively.
S2808 GDC-0068 GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1, Akt2 and Akt3 with IC50 of 5 nM, 18 nM and 8 nM, respectively.
S1558 AT7867 AT7867 is a potent ATP-competitive inhibitor of Akt1/2/3 and S6K with IC50 of 32 nM/17 n/47 nM and 85 nM, respectively.
S8019 AZD5363 AZD5363 is a potent Akt inhibitor for Akt1, Akt2 and Akt3 with IC50 of 3 nM, 8 nM and 8 nM, respectively.
S2743 PF-04691502 PF-04691502 is an ATP-competitive, selective inhibitor of PI3K(α/β/δ/γ)/mTOR with Ki of 1.8 nM/2.1 nM/1.6 nM/1.9 nM and 16 nM, also inhibits Akt phosphorylation on T308/S473 with IC50 of 7.5 nM/3.8 nM.
S1117 Triciribine Triciribine (TCN, API-2) is a DNA synthesis inhibitor and also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM, respectively.
S2635 CCT128930 CCT128930 is a potent, ATP-competitive and selective inhibitor of Akt2 with IC50 of 6 nM.
S2670 A-674563 A-674563 inhibits Akt1, PKA and CDK2 with Ki of 11 nM, 16 nM and 46 nM, respectively.
Cat.No. Product Name Information Product Citations Customer Reviews
S1556 PHT-427 PHT-427 is a dual Akt and PDPK1 inhibitor with Ki of 2.7 μM and 5.2 μM, respectively.
S2310 Honokiol Honokiol is a biphyl neolignan present in the cones, bark, and leaves of Magnolia grandifloris that displays antiangiogenic, antiinflammatory, and antitumor properties due to the inhibitory effect on the PI3K/Akt pathway.
S3056 Miltefosine (Hexadecylphosphocholine) Miltefosine inhibits PI3K/Akt activity with ED50 of 17.2 μM and 8.1 μM in carcinoma cell lines A431 and HeLa.
S2732 Triciribine phosphate (NSC-280594) Triciribine phosphate (TCN-P, NSC-280594, API-2) is a potent Akt inhibitor with IC50 of 130 nM.
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All Akt Inhibitors

Akt, also called RAC (related to protein kinase A and C) or protein kinase B (PKB), is a 57 kD serine/threonine kinases family which is the central mediator of the PI3K pathway with numerous downstream molecules that influence important cellular processes. Akt could be activated by insulin and various growth factors (VGF) in a series of wortmannin-sensitive PI3K cascades [1,2]. Responding to up-stream signaling pathways, Akt is phosphorylated at Thr308 by PDK1[3]and at Ser473 by PDK2 [4,5]. After Akt activation, it could phosphorylate a variety of downstream molecules related to the regulation of cell proliferation including glycogen synthase kinase-3 (GSK-3) [6,7], Bad, PAK1, CREB and p27 [8]and suppress cell apoptosis [9]. Akt directly phosphorylates mTOR in mTORC1, a rapamycin-sensitive complex [10]. Akt could also deactivate tuberin (TSC2), an inhibitor of mTORC1 [11,12]. There are three Akt genes in mammalian genomes, which encode Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ), respectively [13]. All Akt isoforms have similar structural homology. Akt2 has 81% homology with Akt1, and Akt3 83% [14]. All three Akt subtypes are widely expressed in mammalian cells, however Akt 1 is most expressed in brain, heart, and lung, while Akt2 is predominantly located in skeletal muscle and embryonic brown fat and Akt3 is mainly expressed in brain, kidney, and embryonic heart [15-18]. Evidences suggested that Akt is associated with the survival, proliferation, migration and infiltration of many kinds of cancer cells. Perifosine (also KRX-0401), an Akt and PI3K inhibitor, has orphan drug status for the treatment of multiple myeloma and neuroblastoma in the US [19].

References

[1] Burgering, B.M. and P.J. Coffer, Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature, 1995. 376(6541): p. 599-602.
[2] Franke, T.F., et al., The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell, 1995. 81(5): p. 727-36.
[3] Alessi, D.R., et al., Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J, 1996. 15(23): p. 6541-51.
[4] Sarbassov, D.D., et al., Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 2005. 307(5712): p. 1098-101.
[5] Jacinto, E., et al., SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell, 2006. 127(1): p. 125-37.
[6] Cross, D.A., et al., Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature, 1995. 378(6559): p. 785-9.
[7] Lawlor, M.A. and D.R. Alessi, PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci, 2001. 114(Pt 16): p. 2903-10.
[8] Liang, J., et al., PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med, 2002. 8(10): p. 1153-60.
[9] Brazil, D.P., Z.Z. Yang, and B.A. Hemmings, Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci, 2004. 29(5): p. 233-42.
[10] Nave, B.T., et al., Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation. Biochem J, 1999. 344 Pt 2: p. 427-31.
[11] Inoki, K., et al., TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol, 2002. 4(9): p. 648-57.
[12] Manning, B.D., et al., Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell, 2002. 10(1): p. 151-62.
[13] Datta, S.R., A. Brunet, and M.E. Greenberg, Cellular survival: a play in three Akts. Genes Dev, 1999. 13(22): p. 2905-27.
[14] Vanhaesebroeck, B. and D.R. Alessi, The PI3K-PDK1 connection: more than just a road to PKB. Biochem J, 2000. 346 Pt 3: p. 561-76.
[15] Coffer, P.J. and J.R. Woodgett, Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families. Eur J Biochem, 1991. 201(2): p. 475-81.
[16] Altomare, D.A., et al., Cloning, chromosomal localization and expression analysis of the mouse Akt2 oncogene. Oncogene, 1995. 11(6): p. 1055-60.
[17] Altomare, D.A., et al., Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Oncogene, 1998. 16(18): p. 2407-11.
[18] Brodbeck, D., P. Cron, and B.A. Hemmings, A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. J Biol Chem, 1999. 274(14): p. 9133-6.
[19] Yakult Pays Aeterna Zentaris $8.3M for Japanese Rights to Pivotal-Stage Cancer Drug. Genetic Engineering & Biotechnology. Mar 9,2011
 

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