The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells

Qing Chang1, *, Siquan Chen2, Tahua Yang1
1 University of Illinois Technology Innovation Lab and Argos Vision Inc., Chicago, United States
2 Cellular Screening Center, The University of Chicago, Chicago, United States

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 1091
Abstract HTML Views: 426
PDF Downloads: 667
ePub Downloads: 159
Total Views/Downloads: 2343
Unique Statistics:

Full-Text HTML Views: 557
Abstract HTML Views: 300
PDF Downloads: 355
ePub Downloads: 129
Total Views/Downloads: 1341

Creative Commons License
© 2022 Chang et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author University of Illinois Technology Innovation Lab/Argos Vision Inc., 2242 W Harrison St, Suite 201, Chicago, IL 60612, United States; E-mail:



Mitochondrial dysfunction in retinal pigment epithelium (RPE) is a pathogenic factor in age-related macular degeneration (AMD). Improvement of mitochondrial function may ameliorate RPE bioenergetics status, which may in turn nourish the retinal photoreceptors against degenerative loss.


The purpose of this study is to examine the G-protein coupled receptor (GPCR) antagonistic drug CM-20 in modulating mitochondrial function in RPE cells.


Human-derived ARPE-19 cell line was differentiated to improve RPE morphology. Dose response of CM-20 was performed to examine mitochondrial membrane potential (MMP). Secondary validation with multiplexed live-cell mitochondrial imaging was performed. Protection of CM-20 to mitochondria against oxidative stress was detected under co-treatment with hydrogen peroxide.


Treatment with CM-20 elicited a dose-dependent increase of MMP. Multiplexed live-cell mitochondrial imaging showed consistent increase of MMP at an optimal concentration of CM-20 (12.5 µM). MMP was significantly reduced under hydrogen peroxide-induced oxidative stress and treatment with CM-20 showed rescue effects to MMP.


CM-20 increases mitochondrial function and protects mitochondria under oxidative stress. As both GPCRs and mitochondria are potential drug targets, retinal neuroprotective testing of CM-20 is warranted in animal models of retinal degeneration.

Keywords: GPCR, Mitochondria, Polypharmacology, Multi-target drug, RPE, Oxidative stress, Age-related macular degeneration (AMD).