Work

Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy

Year: 2025

Type: review

Abstract: AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival. Small molecule AMPK activators and inhibitors have demonstrated some success in suppressing cancer growth, survival, and drug resistance in preclinical cancer models. In this perspective, we summarize the role of AMPK in cancer and drug resistance, the influence of the tumor microenvironment on AMPK activity, and AMPK activator and inhibitor development. In addition, we discuss the potential importance of isoform-selective targeting of AMPK and approaches for selective AMPK targeting in cancer.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/acs.jmedchem.4c02354

Authors: Juliet E. Strang, Daniel D. Astridge, Vu T. Nguyen, Philip Reigan

Institution: University of Colorado Anschutz

Language: English

Topic: Metabolism, Diabetes, and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500