Development of novel phospholipase A2 inhibitors as an innovative targeted therapy for cancer, in particular leukemia

A recent report entitled «Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A₂α for targeted cancer therapy», published in the prestigious journal Nature Communications, describes the development of novel inhibitors of the enzyme phospholipase A₂ as a targeted therapy for cancer, in particular leukemia.

These novel phospholipase A₂ inhibitors (next generation thiazolyl ketones) were designed, synthesized and developed in the Laboratory of Organic Chemistry (Department of Chemistry, NKUA) from Prof. George Kokotos’ research group. Their study, in collaboration mainly with the Norwegian University of Science and Technology (Norway), but also with the University of California at San Diego (USA), revealed a novel mechanism for the anticancer activity of such inhibitors, suggesting an innovative approach for targeted cancer therapy.

Among the novel compounds, inhibitor GK420 (or AVX420) exhibited potent and selective inhibition of cytosolic phospholipase A₂ (cPLA₂α), 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 acute leukemias and other cancers that are susceptible to oxidative cell death.

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.

George Kokotos, Professor of Organic and Medicinal Chemistry, has extended experience and recognition in the field of the discovery of novel enzyme inhibitors exhibiting pharmacological activity (he is included in the «World’s Top 2% Scientists List»), is inventor in more than 15 patents and has developed and lead various inhibitors to preclinical studies.

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