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Updated: Feb 11, 2026

Manipulation of Rhythmic Food Intake in Mice Using a Custom-Made Feeding System
Published on: December 16, 2022
An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model
Daniel J Price1, David H Drewry2, Lee T Schaller1
1GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Abstract:
Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus-derived cell line, is orally bioavailable, and crosses the blood-brain barrier. When dosed orally in rodents, compound 4 t limited ghrelin-induced food intake.
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