| Autor: |
Anthony Carlo, Matthew S. Dowling, Michael John Munchhof, Robert L. Dow, David Price, Aaron C. Smith, Donna N. Petersen, Athanasia Skoura, Christian Cortes, Allyn T. Londregan, Leonard Buckbinder, Jian Wang, Shenping Liu, Kristen Ford, Samit Kumar Bhattacharya, Paula M. Loria, David Hepworth, Cristiano Ruch Werneck Guimarães, Mark Ammirati, Alan M. Mathiowetz, Wenhua Jiao, Jennifer L. LaPerle, Scott W. Bagley, Ayman El-Kattan, Suvi T. M. Orr, Rebecca Conrad |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
ACS Medicinal Chemistry Letters. 6:1128-1133 |
| ISSN: |
1948-5875 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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