Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy-Reference-Cited by-同舟云学术

Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy

Published:2017-08-04 Issue:6350 Volume:357 Page:507-511
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Myers Robert W.¹^ORCID,Guan Hong-Ping²^ORCID,Ehrhart Juliann³,Petrov Aleksandr²,Prahalada Srinivasa³^ORCID,Tozzo Effie²^ORCID,Yang Xiaodong²,Kurtz Marc M.¹^ORCID,Trujillo Maria⁴^ORCID,Gonzalez Trotter Dinko⁵,Feng Danqing⁶,Xu Shiyao⁷,Eiermann George⁴,Holahan Marie A.⁵^ORCID,Rubins Daniel⁵^ORCID,Conarello Stacey⁴,Niu Xiaoda¹,Souza Sandra C.²^ORCID,Miller Corin⁵,Liu Jinqi²^ORCID,Lu Ku²,Feng Wen¹,Li Ying²^ORCID,Painter Ronald E.¹,Milligan James A.¹^ORCID,He Huaibing⁷^ORCID,Liu Franklin²^ORCID,Ogawa Aimie¹,Wisniewski Douglas¹^ORCID,Rohm Rory J.²,Wang Liyang¹,Bunzel Michelle⁵^ORCID,Qian Ying²,Zhu Wei²^ORCID,Wang Hongwu⁶,Bennet Bindu³^ORCID,LaFranco Scheuch Lisa³^ORCID,Fernandez Guillermo E.³,Li Cai⁴,Klimas Michael⁵^ORCID,Zhou Gaochao¹^ORCID,van Heek Margaret⁴,Biftu Tesfaye⁶^ORCID,Weber Ann⁶^ORCID,Kelley David E.²^ORCID,Thornberry Nancy²,Erion Mark D.²,Kemp Daniel M.²,Sebhat Iyassu K.⁶^ORCID

Affiliation:

1. In Vitro Pharmacology, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

2. Biology-Discovery, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

3. Safety Assessment and Laboratory Animal Resources, Merck Research Laboratories, West Point, PA 19486, USA.

4. In Vivo Pharmacology, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

5. Translational Imaging and Biomarkers Departments, Merck Research Laboratories, West Point, PA 19486, USA.

6. Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

7. PPDM Preclinical ADME Departments, Merck Research Laboratories, Kenilworth, NJ 07033, USA.

Abstract

Hitting a dozen enzymes with one drug The adenosine monophosphate-activated protein kinase (AMPK) controls cellular energy status. AMPK is activated when energy levels fall. This stimulates adenosine triphosphate (ATP)-generating pathways that promote glucose uptake and inhibits ATP-consuming pathways associated with glucose synthesis. In principle, these effects would be beneficial in metabolic diseases, including diabetes. Pharmacological activation of AMPK has been challenging, however, because in mammals, the enzyme exists as 12 distinct complexes. Myers et al. describe an orally available compound (MK-8722) that activates all 12 complexes (see the Perspective by Hardie). In animal models, MK-8722 ameliorated diabetes, but it also caused enlargement of the heart. MK-8722 may be a useful tool compound for laboratory research on AMPK function. Science , this issue p. 507 ; see also p. 455

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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