2. Academic Validation
  3. Inhibiting NF-κB-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures

Inhibiting NF-κB-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.
Kexue Li 1,  Lawrence R McGee,  Ben Fisher,  Athena Sudom,  Jinsong Liu,  Steven M Rubenstein,  Mohmed K Anwer,  Timothy D Cushing,  Youngsook Shin,  Merrill Ayres,  Fei Lee,  John Eksterowicz,  Paul Faulder,  Bohdan Waszkowycz,  Olga Plotnikova,  Ellyn Farrelly,  Shou-Hua Xiao,  Guoqing Chen,  Zhulun Wang
Affiliations

Affiliation

  • 1 Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. [email protected]
PMID: 23374866 DOI: 10.1016/j.bmcl.2013.01.012
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.

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