5DI1

MAP4K4 in complex with an inhibitor

5DI1 の概要

• エントリーDOI: 10.2210/pdb5di1/pdb
• 関連するPDBエントリー: 4ZP5
• 分子名称: Mitogen-activated protein kinase kinase kinase kinase 4, 4-{6-amino-5-[4-(methylsulfonyl)phenyl]pyridin-3-yl}phenol (3 entities in total)
• 機能のキーワード: kinase, inhibitor, complex, medicinal chemistry, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : O95819
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71237.80

構造登録者

Liu, S. (登録日: 2015-08-31, 公開日: 2016-01-13, 最終更新日: 2023-09-27)

主引用文献

Ammirati, M.,Bagley, S.W.,Bhattacharya, S.K.,Buckbinder, L.,Carlo, A.A.,Conrad, R.,Cortes, C.,Dow, R.L.,Dowling, M.S.,El-Kattan, A.,Ford, K.,Guimaraes, C.R.,Hepworth, D.,Jiao, W.,LaPerle, J.,Liu, S.,Londregan, A.,Loria, P.M.,Mathiowetz, A.M.,Munchhof, M.,Orr, S.T.,Petersen, D.N.,Price, D.A.,Skoura, A.,Smith, A.C.,Wang, J.
Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment.
Acs Med.Chem.Lett., 6:1128-1133, 2015

PubMed Abstract: Recent studies in adipose tissue, pancreas, muscle, and macrophages suggest that MAP4K4, a serine/threonine protein kinase may be a viable target for antidiabetic drugs. As part of the evaluation of MAP4K4 as a novel antidiabetic target, a tool compound, 16 (PF-6260933) and a lead 17 possessing excellent kinome selectivity and suitable properties were delivered to establish proof of concept in vivo. The medicinal chemistry effort that led to the discovery of these lead compounds is described herein together with in vivo pharmacokinetic properties and activity in a model of insulin resistance.

PubMed: 26617966
DOI: 10.1021/acsmedchemlett.5b00215

実験手法

X-RAY DIFFRACTION (2.9 Å)