5DI1

MAP4K4 in complex with an inhibitor

Summary for 5DI1

• Entry DOI: 10.2210/pdb5di1/pdb
• Related: 4ZP5
• Descriptor: Mitogen-activated protein kinase kinase kinase kinase 4, 4-{6-amino-5-[4-(methylsulfonyl)phenyl]pyridin-3-yl}phenol (3 entities in total)
• Functional Keywords: kinase, inhibitor, complex, medicinal chemistry, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : O95819
• Total number of polymer chains: 2
• Total formula weight: 71237.80

Authors

Liu, S. (deposition date: 2015-08-31, release date: 2016-01-13, Last modification date: 2023-09-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)