Publications by authors named "Alice Grabbe"
Inhibition of NF-κB inducing kinase (NIK) has been pursued as a promising therapeutic target for autoimmune disorders due to its highly regulated role in key steps of the NF-κB signaling pathway. Previously reported NIK inhibitors from our group were shown to be potent, selective, and efficacious, but had higher human dose projections than desirable for immunology indications. Herein we report the clearance-driven optimization of a NIK inhibitor guided by metabolite identification studies and structure-based drug design.
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- NF-κB-inducing kinase (NIK) plays a key role in the noncanonical NF-κB pathway, affecting processes like B cell maturation and dendritic cell activation.
- Researchers identified a series of potent NIK inhibitors using a scaffold-hopping strategy combined with structure-based design, focusing on optimizing chemical properties.
- One of the top compounds, 4f, demonstrated effective inhibition of B cell survival linked to BAFF in lab tests, and it showed a favorable pharmacokinetic profile across different species in vivo.