Contribution of Assist. Professor Maroula Kokotou to the development of novel phospholipase A2 inhibitors as an innovative targeted therapy for cancer, in particular leukemia

Assistant Professor Maroula Kokotou (Laboratory of Chemistry, Department of Food Science and Human Nutrition, Agricultural University of Athens) is a coauthor in a recent paper entitled «Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A2α for targeted cancer therapy», which has been published in the prestigious journal Nature Communications, and describes the development of novel inhibitors of the enzyme phospholipase A2 as a targeted therapy for cancer, in particular leukemia.

The development of novel phospholipase A2 inhibitors (next generation thiazolyl ketones) and their study are a result of cooperation between the Department of Chemistry, National and Kapodistrian University of Athens, the Norwegian University of Science and Technology (Norway), the University of California at San Diego (USA), the Kobe University (Japan) and the Agricultural University of Athens.

Inhibitor GK420 (or AVX420) exhibited potent and selective inhibition of cytosolic phospholipase A2 and a variety of cancer cell lines. These findings imply cPLA2α may support cancer by mitigating oxidative stress and inhibiting tumor suppressor expression and suggest that GK420 has potential for treating cancers that are susceptible to oxidative cell death. Assist. Prof. M. Kokotou contributed to the study of the stability of inhibitors in human plasma and the study of the mechanism of action of inhibitor, where LC-HRMS suggested the action as a prodrug.

According to press release, Coegin Pharma (Sweden) is now planning to conduct the final preclinical tests to assess safety, establish the correct dosage and determine the best method for administering GK420, in order to initiate clinical trials in humans.

Link: https://www.nature.com/articles/s41467-024-55536-9.