A-443654   Click here for help

GtoPdb Ligand ID: 8204

Synonyms: A 443654 | A443654
PDB Ligand
Compound class: Synthetic organic
Comment: A-443654 is an ATP-competitive inhibitor of all three Akt (protein kinase B) subtypes [2], but causes paradixical hyperphosphorylation of two regulatory amino acid residues (Thr308 and Ser473) of the Akt protein [1,3]. A-443654 exhibits modest selectivity for Akt, compared to other AGC family kinases, such as PKA and PKC [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 92.61
Molecular weight 397.19
XLogP 4.17
No. Lipinski's rules broken 0
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Canonical SMILES NC(Cc1c[nH]c2c1cccc2)COc1cncc(c1)c1ccc2c(c1)c(C)n[nH]2
Isomeric SMILES N[C@@H](Cc1c[nH]c2c1cccc2)COc1cncc(c1)c1ccc2c(c1)c(C)n[nH]2
InChI InChI=1S/C24H23N5O/c1-15-22-10-16(6-7-24(22)29-28-15)17-9-20(13-26-11-17)30-14-19(25)8-18-12-27-23-5-3-2-4-21(18)23/h2-7,9-13,19,27H,8,14,25H2,1H3,(H,28,29)/t19-/m0/s1
1. Han EK, Leverson JD, McGonigal T, Shah OJ, Woods KW, Hunter T, Giranda VL, Luo Y. (2007)
Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition.
Oncogene, 26 (38): 5655-61. [PMID:17334390]
2. 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]
3. Okuzumi T, Fiedler D, Zhang C, Gray DC, Aizenstein B, Hoffman R, Shokat KM. (2009)
Inhibitor hijacking of Akt activation.
Nat Chem Biol, 5 (7): 484-93. [PMID:19465931]