4GV1

PKB alpha in complex with AZD5363

Summary for 4GV1

• Entry DOI: 10.2210/pdb4gv1/pdb
• Descriptor: RAC-alpha serine/threonine-protein kinase, 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: protein kinase, 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: 40191.15

Authors

Addie, M.,Ballard, P.,Bird, G.,Buttar, D.,Currie, G.,Davies, B.,Debreczeni, J.,Dry, H.,Dudley, P.,Greenwood, R.,Hatter, G.,Jestel, A.,Johnson, P.D.,Kettle, J.G.,Lane, C.,Lamont, G.,Leach, A.,Luke, R.W.A.,Ogilvie, D.,Page, K.,Pass, M.,Steinbacher, S.,Steuber, H.,Pearson, S.,Ruston, L. (deposition date: 2012-08-30, release date: 2013-02-27, Last modification date: 2024-10-16)

Primary citation

Addie, M.,Ballard, P.,Buttar, D.,Crafter, C.,Currie, G.,Davies, B.R.,Debreczeni, J.,Dry, H.,Dudley, P.,Greenwood, R.,Johnson, P.D.,Kettle, J.G.,Lane, C.,Lamont, G.,Leach, A.,Luke, R.W.,Morris, J.,Ogilvie, D.,Page, K.,Pass, M.,Pearson, S.,Ruston, L.
Discovery of 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases.
J.Med.Chem., 56:2059-2073, 2013

PubMed Abstract: Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.

PubMed: 23394218
DOI: 10.1021/jm301762v

Experimental method

X-RAY DIFFRACTION (1.49 Å)