3QKK

Spirochromane Akt Inhibitors

Summary for 3QKK

• Entry DOI: 10.2210/pdb3qkk/pdb
• Related: 3OCB 3QKL 3QKM
• Descriptor: RAC-alpha serine/threonine-protein kinase, Glycogen synthase kinase-3 beta, N-(2-ethoxyethyl)-N-{(2S)-2-hydroxy-3-[(2R)-6-hydroxy-4-oxo-3,4-dihydro-1'H-spiro[chromene-2,3'-piperidin]-1'-yl]propyl}-2,6-dimethylbenzenesulfonamide, ... (4 entities in total)
• Functional Keywords: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P31749
• Total number of polymer chains: 2
• Total formula weight: 41136.86

Authors

Kallan, N.C.,Spencer, K.L.,Blake, J.F.,Xu, R.,Heizer, J.,Bencsik, J.R.,Mitchell, I.S.,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: 2011-03-30, Last modification date: 2024-10-16)

Primary citation

Kallan, N.C.,Spencer, K.L.,Blake, J.F.,Xu, R.,Heizer, J.,Bencsik, J.R.,Mitchell, I.S.,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 and SAR of spirochromane Akt inhibitors.
Bioorg.Med.Chem.Lett., 21:2410-2414, 2011

PubMed Abstract: A novel series of spirochromane pan-Akt inhibitors is reported. SAR optimization furnished compounds with improved enzyme potencies and excellent selectivity over the related AGC kinase PKA. Attempted replacement of the phenol hinge binder provided compounds with excellent Akt enzyme and cell activities but greatly diminished selectivity over PKA.

PubMed: 21392984
DOI: 10.1016/j.bmcl.2011.02.073

Experimental method

X-RAY DIFFRACTION (2.3 Å)