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Updated: Feb 15, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
Discovery of MK-8722: A Systemic, Direct Pan-Activator of AMP-Activated Protein Kinase
Danqing Feng1, Tesfaye Biftu1, F Anthony Romero1
1Medicinal Chemistry, PPDM Preclinical ADME, In Vitro Pharmacology, In Vivo Pharmacology, and Biology-Discovery Departments, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
Abstract:
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of mammalian energy homeostasis and has been implicated in mediating many of the beneficial effects of exercise and weight loss including lipid and glucose trafficking. As such, the enzyme has long been of interest as a target for the treatment of Type 2 Diabetes Mellitus. We describe the optimization of β1-selective, liver-targeted AMPK activators and their evolution into systemic pan-activators capable of acutely lowering glucose in mouse models. Identifying surrogates for the key acid moiety in early generation compounds proved essential in improving β2-activation and in balancing improvements in plasma unbound fraction while avoiding liver sequestration.
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