Piclidenoson is a First-in-Class and Orally Active A3AR Agonist

One of the main strategies for cancer research is the identification of drugs that can cause apoptotic death in malignant cells. Additionally, Adenosine 5′-triphosphate (ATP), UTP, and adenosine are considered that inhibit the growth of several cancerous cell lines.

Adenosine has several physiological and pharmacological functions. It can modulate cell proliferation, inhibit cell growth, and induce apoptosis in various cancer cell types. Additionally, the effects of adenosine are related to its interaction with adenosine receptors containing four subtypes: A1R, A2AR, A2BR, and A3R.

In this article, we will introduce an orally active A3 adenosine receptor (A3AR) agonist, Piclidenoson.

Piclidenoson is a First in Class and Orally Active A3AR Agonist 2021 02 11 - Piclidenoson is a First-in-Class and Orally Active A3AR Agonist

Piclidenoson is a first-in-class and selective A3AR agonist. Besides, it exhibits an antiproliferative effect and induces apoptosis in different cancer cell types.

In vitro, in OVCAR-3 cells, Piclidenoson is able to inhibit forskolin-stimulated cAMP levels with an EC50 of 0.82 μM. Besides, it also inhibits forskolin-stimulated cAMP levels with an EC50 of 1.2 μM in Caov-4 cells.
In a cell proliferation assay, Piclidenoson shows antiproliferative effect in human ovarian cancer cell lines. The IC50 values are 32.14 μM and 45.37 μM for OVCAR-3 and Caov-4 cells, respectively.
Furthermore, at a dose ranging from 0.0001 μM to 100 μM, Piclidenoson reduces cell viability in a dose-dependent manner.

Furthermore, Piclidenoson significant increases in the percentage of apoptosis in a concentration-dependent manner. It decreases the expression of Bcl-2 noticeably. And it also increases the expression of Bax protein. As a result, Piclidenoson induces apoptosis via the mitochondrial signaling pathway.

In B10CBAF1 male mice aged 3 months (average 30 g). Piclidenoson results in statistically significant increases of the mean survival time in comparison with the control irradiated mice.

Besides, Piclidenoson is an active anti-inflammatory agent. It acts after binding to the G protein associated with A3AR and induces a robust anti-inflammatory effect. Therefore, Piclidenoson can be used for the research of autoimmune inflammatory diseases and COVID-19.

In conclusion, Piclidenoson, as a potent A3 adenosine receptor agonist, has the potential for cancer and autoimmune inflammatory disease research.


[1]. Abedi H, et al. Tumour Biol. 2014 Nov;35(11):11027-11039.

[2]. Chandan Sarkar, et al. Front Pharmacol. 2020; 11: 572870.