(NIK, MAP3K14), is a key regulator in the non-canonical NF-kB pathway which is central to multiple autoimmune and inflammatory disorders biology.  Accordingly, modulation of this pathway and inhibition of NIK is an attractive strategy that has generated substantial interest for pharmaceutical companies including Takeda. Our method to targeting NIK was centered around fragment-based approaches aimed at producing highly efficient inhibitors with superior physiochemical properties.  A fragment-based screen against the target was performed using STD NMR and thermal shift assays which resulted in identification &gt;90 hits. The subsequent optimization of a prioritized fragment to a novel lead compound with high ligand efficiency, adequate cellular potency and good physiochemical properties will be presented.<br/>

Discovery of novel inhibitors of NF-kB Inducing Kinase (NIK) from an FBDD approach

253rd National Meeting (2017)

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