6CMJ

Human CAMKK2 with GSK650393

6CMJ の概要

• エントリーDOI: 10.2210/pdb6cmj/pdb
• 分子名称: Calcium/calmodulin-dependent protein kinase kinase 2, 2-(2-methylpropyl)-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid, FORMIC ACID, ... (5 entities in total)
• 機能のキーワード: kinase, signaling protein, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : Q96RR4
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74628.44

構造登録者

Williams, S.P.,Reid, R.A.,Price, D.J.,Drewry, D.H. (登録日: 2018-03-05, 公開日: 2018-04-04, 最終更新日: 2024-11-20)

主引用文献

Price, D.J.,Drewry, D.H.,Schaller, L.T.,Thompson, B.D.,Reid, P.R.,Maloney, P.R.,Liang, X.,Banker, P.,Buckholz, R.G.,Selley, P.K.,McDonald, O.B.,Smith, J.L.,Shearer, T.W.,Cox, R.F.,Williams, S.P.,Reid, R.A.,Tacconi, S.,Faggioni, F.,Piubelli, C.,Sartori, I.,Tessari, M.,Wang, T.Y.
An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model.
Bioorg. Med. Chem. Lett., 28:1958-1963, 2018

PubMed 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.

PubMed: 29653895
DOI: 10.1016/j.bmcl.2018.03.034

実験手法

X-RAY DIFFRACTION (2.4 Å)