3ULI

Human Cyclin Dependent Kinase 2 (CDK2) bound to azabenzimidazole derivative

Summary for 3ULI

• Entry DOI: 10.2210/pdb3uli/pdb
• Descriptor: Cyclin-dependent kinase 2, 1-(aminomethyl)-N-(3-{[6-bromo-2-(4-methoxyphenyl)-3H-imidazo[4,5-b]pyridin-7-yl]amino}propyl)cyclopropanecarboxamide (3 entities in total)
• Functional Keywords: azabenzimidazole derivative, phosphotransfer, complex with cyclin a or cyclin e, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• Total number of polymer chains: 1
• Total formula weight: 34449.85

Authors

Larsen, N.A.,Tucker, J.A.,Wang, T. (deposition date: 2011-11-10, release date: 2013-08-14, Last modification date: 2024-02-28)

Primary citation

Wang, T.,Block, M.A.,Cowen, S.,Davies, A.M.,Devereaux, E.,Gingipalli, L.,Johannes, J.,Larsen, N.A.,Su, Q.,Tucker, J.A.,Whitston, D.,Wu, J.,Zhang, H.J.,Zinda, M.,Chuaqui, C.
Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKK epsilon kinases.
Bioorg.Med.Chem.Lett., 22:2063-2069, 2012

PubMed Abstract: The design, synthesis and biological evaluation of a series of azabenzimidazole derivatives as TBK1/IKKε kinase inhibitors are described. Starting from a lead compound 1a, iterative design and SAR exploitation of the scaffold led to analogues with nM enzyme potencies against TBK1/IKKε. These compounds also exhibited excellent cellular activity against TBK1. Further structure-based design to improve selectivity over CDK2 and Aurora B resulted in compounds such as 5b-e. These probe compounds will facilitate study of the complex cancer biology of TBK1 and IKKε.

PubMed: 22305584
DOI: 10.1016/j.bmcl.2012.01.018

Experimental method

X-RAY DIFFRACTION (2 Å)