5AAD

Aurora A kinase bound to an imidazopyridine inhibitor (7a)

Summary for 5AAD

• Entry DOI: 10.2210/pdb5aad/pdb
• Related: 5AAE 5AAF 5AAG
• Descriptor: AURORA KINASE A, 7-(1-benzyl-1H-pyrazol-4-yl)-6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine, SULFATE ION, ... (4 entities in total)
• Functional Keywords: transferase, aurora-a, imidazopyridine, aurora kinase, inhibitor
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: O14965
• Total number of polymer chains: 1
• Total formula weight: 33480.65

Authors

McIntyre, P.J.,Kosmopoulou, M.,Bayliss, R. (deposition date: 2015-07-24, release date: 2015-09-02, Last modification date: 2024-01-10)

Primary citation

Bavetsias, V.,Perez-Fuertes, Y.,Mcintyre, P.J.,Atrash, B.,Kosmopoulou, M.,O'Fee, L.,Burke, R.,Sun, C.,Faisal, A.,Bush, K.,Avery, S.,Henley, A.,Raynaud, F.I.,Linardopoulos, S.,Bayliss, R.,Blagg, J.
7-(Pyrazol-4-Yl)-3H-Imidazo[4,5-B]Pyridine-Based Derivatives for Kinase Inhibition: Co-Crystallisation Studies with Aurora-A Reveal Distinct Differences in the Orientation of the Pyrazole N1-Substituent.
Bioorg.Med.Chem.Lett., 25:4203-, 2015

PubMed Abstract: Introduction of a 1-benzyl-1H-pyrazol-4-yl moiety at C7 of the imidazo[4,5-b]pyridine scaffold provided 7a which inhibited a range of kinases including Aurora-A. Modification of the benzyl group in 7a, and subsequent co-crystallisation of the resulting analogues with Aurora-A indicated distinct differences in binding mode dependent upon the pyrazole N-substituent. Compounds 7a and 14d interact with the P-loop whereas 14a and 14b engage with Thr217 in the post-hinge region. These crystallographic insights provide options for the design of compounds interacting with the DFG motif or with Thr217.

PubMed: 26296477
DOI: 10.1016/J.BMCL.2015.08.003

Experimental method

X-RAY DIFFRACTION (3.1 Å)