Modified Thiazole Benzenesulfonamide Demonstrates Anticancer Activity in Melanoma

A newly discovered synthesized drug, HA15, reduced the viability of melanoma cells without affecting normal cells in cell culture and mouse xenograft models of the disease. HA15 is a type of thiazole benzenesulfonamide.1

Melanoma is an aggressive skin cancer that affects the melanocytes that generate the skin pigmentation molecule melanin. The disease has 3 stages of tumor progression: radial growth, the cancerous cells chaotically proliferate in the epidermis; vertical growth, diseased cells invade the dermis; metastatic stage, the cancerous cells mobilize and invade peripheral tissues.

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The use of targeted therapies and immunotherapies have shown encouraging results for treating the metastatic stage of melanoma, but most patients will need additional therapies to inhibit tumors from returning and to limit more metastases. Due to the rapidly increasing incidence of melanoma, identifying new treatment options has become essential for effective treatment of this disease.

This study, published in Cancer Cell, discovered that the thiazole benzenesulfonamides have anticancer properties.

"Initially this family of drugs was identified in type 2 diabetes, as it increased the sensitivity of cells to insulin. If we wanted to use it against cancer, we had to be able to eliminate this pro-insulin activity," said senior author Stéphane Rocchi, PhD, INSERM, Paris, France.

"Thus we started to modify its structure."

Collaborating with researchers at the Nice Institute of Chemistry, Nice, France, researchers were able to modify the thiazole benzenesulfonamide structure to remove the pro-insulin activity. The most promising thiazole benzenesulfonamide that emerged was HA15.

In cell cultures from patients with melanoma whose disease developed resistance to BRAF inhibitors, HA15 exhibited anticancer activity. BRAF is a proto-oncogene that promotes cell proliferation. In a mouse xenograft model of melanoma, HA15 was effective against BRAF inhibitor-resistant and inhibitor-sensitive tumors.

Reference

1. Cerezo M, Lehraiki A, Millet A, et al. Compounds triggering ER stress exert anti-melanoma effects and evercome BRAF inhibitor resistance [published online May 19, 2016]. Cancer Cell. doi:10.1016/j.ccell.2016.04.013.
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