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Updated: Jun 25, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
Novel tricyclic inhibitors of IkappaB kinase
James Kempson1, Steven H Spergel, Junqing Guo
1Departments of Discovery Chemistry, Discovery Biology, and Metabolism and Pharmacokinetics and Synthesis and Analysis Technology Team, Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543-4000, USA.
Abstract:
The design and synthesis of a novel series of oxazole-, thiazole-, and imidazole-based inhibitors of IkappaB kinase (IKK) are reported. Biological activity was improved compared to the pyrazolopurine lead, and the expedient synthesis of the new tricyclic systems allowed for efficient exploration of structure-activity relationships. This, combined with an iterative rat cassette dosing strategy, was used to identify compounds with improved pharmacokinetic (PK) profiles to advance for in vivo evaluation.
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