3QKM

Spirocyclic sulfonamides as AKT inhibitors

Summary for 3QKM

• Entry DOI: 10.2210/pdb3qkm/pdb
• Related: 3OCB
• Descriptor: RAC-alpha serine/threonine-protein kinase, N-(2-ethoxyethyl)-N-{(2S)-2-hydroxy-3-[(5R)-2-(quinazolin-4-yl)-2,7-diazaspiro[4.5]dec-7-yl]propyl}-2,6-dimethylbenzenesulfonamide (3 entities in total)
• Functional Keywords: kinase domain, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P31749
• Total number of polymer chains: 1
• Total formula weight: 40048.74

Authors

Xu, R.,Banka, A.,Blake, J.F.,Mitchell, I.S.,Wallace, E.M.,Gloor, S.L.,Martinson, M.,Risom, T.,Gross, S.D.,Morales, T.,Vigers, G.P.A.,Brandhuber, B.J.,Skelton, N.J. (deposition date: 2011-02-01, release date: 2011-04-06, Last modification date: 2024-10-30)

Primary citation

Xu, R.,Banka, A.,Blake, J.F.,Mitchell, I.S.,Wallace, E.M.,Bencsik, J.R.,Kallan, N.C.,Spencer, K.L.,Gloor, S.L.,Martinson, M.,Risom, T.,Gross, S.D.,Morales, T.H.,Wu, W.I.,Vigers, G.P.,Brandhuber, B.J.,Skelton, N.J.
Discovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA.
Bioorg.Med.Chem.Lett., 21:2335-2340, 2011

PubMed Abstract: We describe the design and synthesis of novel bicyclic spiro sulfonamides as potent Akt inhibitors. Through structure-based rational design, we have successfully improved PKA selectivity of previously disclosed spirochromanes. Representative compounds showed favorable Akt potency while exhibiting up to 1000-fold selectivity against PKA.

PubMed: 21420856
DOI: 10.1016/j.bmcl.2011.02.098

Experimental method

X-RAY DIFFRACTION (2.2 Å)