Drug Class Inhibits Dual Molecular Targets Simultaneously, Improving Cancer Treatment

A potential new anti-cancer drug class may optimize therapeutic safety and efficacy by inhibiting 2 or more molecular targets at once, according to a study published in the Proceedings of the National Academy of Sciences.

“Most anti-cancer drugs have a single target,” said co-senior author Donald L. Durden, MD, PhD. “They try to do one thing, such as block a single receptor or signaling pathway. This paper is proof-of-concept of a completely different mode of drug discovery clearly separated from the standard practice of 1 drug, 1 target.”

The investigators used a molecular modeling crystal structure along with nuclear magnetic resonance imaging to engineer the SF2523 molecule in silico to disrupt 2 key MYC-mediating factors simultaneously. The 2 factors—–PI3K and BRD4–– promote cancer cell growth.

The results of the study showed SF2523 concomitantly inhibited PI3K and BRD4 in cell and mouse models, blocking MYC activation and expression. The approach inhibited cancer growth and metastasis with less toxicity to the host, and improved efficacy.

“This is a ’first in class’ approach to achieve a maximum inhibition of MYC in the treatment of the multitude of cancers known to be driven by the MYC oncogene,” Durden said. “These findings suggest that dual-activity inhibitors are a highly promising lead compound for developing new anti-cancer therapeutics.”