| Structural highlights
Publication Abstract from PubMed
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.
Inhibiting NF-kappaB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures.,Li K, McGee LR, Fisher B, Sudom A, Liu J, Rubenstein SM, Anwer MK, Cushing TD, Shin Y, Ayres M, Lee F, Eksterowicz J, Faulder P, Waszkowycz B, Plotnikova O, Farrelly E, Xiao SH, Chen G, Wang Z Bioorg Med Chem Lett. 2013 Mar 1;23(5):1238-44. doi: 10.1016/j.bmcl.2013.01.012. , Epub 2013 Jan 11. PMID:23374866[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Li K, McGee LR, Fisher B, Sudom A, Liu J, Rubenstein SM, Anwer MK, Cushing TD, Shin Y, Ayres M, Lee F, Eksterowicz J, Faulder P, Waszkowycz B, Plotnikova O, Farrelly E, Xiao SH, Chen G, Wang Z. Inhibiting NF-kappaB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1238-44. doi: 10.1016/j.bmcl.2013.01.012. , Epub 2013 Jan 11. PMID:23374866 doi:http://dx.doi.org/10.1016/j.bmcl.2013.01.012
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