GPR55 Agonism

An agonist that binds to a GPR55 receptor is a compound or drug that binds to the receptor and produces an expected effect (see below).

GPR55 Agonism Associated Effects

GPR55/LPI and Cancer

GPR55/LPI axis is considered a novel target for cancer therapeutics (R. Ross, 2011).¹

GPR55 overexpression has been associated with cancer metastasis in specific tumors such as acute myeloid leukemia, uveal melanoma, low-grade glioma, and renal cancer. Furthermore, the LPI/GPR55 axis has been reported to participate in several pro-oncogenic processes, such as cellular proliferation, differentiation, migration, invasion, and metastasis (A. Calvillo-Robledo et al., 2022).²

GPR55/LPI may play an essential role in the metastasis of breast cancer cells (L. Ford et al., 2010).³

Cancer cells may be able to hijack the motility-related activity of GPR55 and increase LPI production, both associated with metastasis (A. Wnorowski et al., 2021).⁴

Expression of GPR55 is increased in endometrial carcinoma (T. Ayakannu et al., 2021).⁵

The reader is reminded that THC is an agonist at GPR55 while CBD is an antagonist at the same receptor with potential practical relevance in the clinical oncology setting.

GPR55/LPI and Other Conditions

GPR55/LPI axis also potentially influences obesity (J. Moreno-Navarrete et al., 2012).⁶

More specifically, activation of the LPI/GPR55 axis may contribute to the underlying pathology of obesity-induced inflammation (M. Kurano et al., 2021).⁷ Also, GPR55 plays a role in descending pain modulation associated with inflammatory pains (H. Blanton et al., 2022).⁸

GPR55 affects osteoclast and osteoblast differentiation associated with the development of bone mass (L. Whyte et al., 2009)⁹ with potential relevance to antagonists in treating osteoporosis.

GPR55 Agonists

In 2009 another UK team found that lysophosphatidylinositol (LPI) was a potent and efficacious ligand at GPR55 (C. Henstridge et al., 2009).¹⁰

Strong GPR55 agonists (E. Ryberg et al., 2007)¹¹

• 2-AG EC₅₀ ~2nM
• Anandamide EC₅₀ ~18nM
• CP55940 ~5nM
• Noladin ether ~10nM
• Palmitoylethanolamide (PEA) ~4nM
• THC EC₅₀ ~8nM
• Virodhamine EC₅₀ ~12nM