1030610-61-7Relevant articles and documents
An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model
Price, Daniel J.,Drewry, David H.,Schaller, Lee T.,Thompson, Brian D.,Reid, Paul R.,Maloney, Patrick R.,Liang, Xi,Banker, Periette,Buckholz, Richard G.,Selley, Paula K.,McDonald, Octerloney B.,Smith, Jeffery L.,Shearer, Todd W.,Cox, Richard F.,Williams, Shawn P.,Reid, Robert A.,Tacconi, Stefano,Faggioni, Federico,Piubelli, Chiara,Sartori, Ilaria,Tessari, Michela,Wang, Tony Y.
, p. 1958 - 1963 (2018/04/20)
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.
