Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment.
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ABSTRACT:
SUBMITTER: Ammirati M
PROVIDER: S-EPMC4645242 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment.
Ammirati Mark M Bagley Scott W SW Bhattacharya Samit K SK Buckbinder Leonard L Carlo Anthony A AA Conrad Rebecca R Cortes Christian C Dow Robert L RL Dowling Matthew S MS El-Kattan Ayman A Ford Kristen K Guimarães Cristiano R W CR Hepworth David D Jiao Wenhua W LaPerle Jennifer J Liu Shenping S Londregan Allyn A Loria Paula M PM Mathiowetz Alan M AM Munchhof Michael M Orr Suvi T M ST Petersen Donna N DN Price David A DA Skoura Athanasia A Smith Aaron C AC Wang Jian J
ACS medicinal chemistry letters 20151006 11
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 her ...[more]
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