4IDV

Crystal Structure of NIK with compound 4-{3-[2-amino-5-(2-methoxyethoxy)pyrimidin-4-yl]-1H-indol-5-yl}-2-methylbut-3-yn-2-ol (13V)

Summary for 4IDV

• Entry DOI: 10.2210/pdb4idv/pdb
• Related: 4IDT
• Descriptor: Mitogen-activated protein kinase kinase kinase 14, 4-{3-[2-amino-5-(2-methoxyethoxy)pyrimidin-4-yl]-1H-indol-5-yl}-2-methylbut-3-yn-2-ol (3 entities in total)
• Functional Keywords: nik, nuclear factor (nf)-kb, p100 processing, 2-aminopyrimidine, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q99558
• Total number of polymer chains: 4
• Total formula weight: 158048.47

Authors

Liu, J.,Sudom, A.,Wang, Z. (deposition date: 2012-12-13, release date: 2013-04-17, Last modification date: 2024-02-28)

Primary citation

Li, K.,McGee, L.R.,Fisher, B.,Sudom, A.,Liu, J.,Rubenstein, S.M.,Anwer, M.K.,Cushing, T.D.,Shin, Y.,Ayres, M.,Lee, F.,Eksterowicz, J.,Faulder, P.,Waszkowycz, B.,Plotnikova, O.,Farrelly, E.,Xiao, S.H.,Chen, G.,Wang, Z.
Inhibiting NF-KB-inducing kinase (NIK): Discovery, structure-based design, synthesis, structure activity relationship, and co-crystal structures
Bioorg.Med.Chem.Lett., 23:1238-1244, 2013

PubMed Abstract: The discovery, structure-based design, synthesis, and optimization of NIK inhibitors are described. Our work began with an HTS hit, imidazopyridinyl pyrimidinamine 1. We utilized homology modeling and conformational analysis to optimize the indole scaffold leading to the discovery of novel and potent conformationally constrained inhibitors such as compounds 25 and 28. Compounds 25 and 31 were co-crystallized with NIK kinase domain to provide structural insights.

PubMed: 23374866
DOI: 10.1016/j.bmcl.2013.01.012

Experimental method

X-RAY DIFFRACTION (2.9 Å)