Anti-Tumor Drug Shows Potency Across Multiple Cancer Types


Uncialamycin may effectively treat various cancer types, including gastric, lung, and ovarian cancers.

The production of a potent anti-tumor antibiotic has been streamlined and improved by a team of researchers at Rice University, and could potentially be used to fight cancer.

Uncialamycin is an enediyne, which are compounds defined by the presence of 9- and 10-member atomic rings in their structures. Published in the Journal of the American Chemical Society, the total synthesis of uncialamycin was streamlined to make it easier to create novel variations of the molecule that would allow it to be used as a useful cancer-fighting drug too toxic in its original form.

“The 10-member ring is like the warhead of the molecule,” said researcher K.C. Nicolaou. “The ring undergoes the Bergman reaction, producing radicals that cut both strands of the DNA, rendering it difficult to repair by the cell. It's a Trojan horse that gets inside the cell and causes havoc.”

For the study, scientists synthesized pure synthetic uncialamycin, as well as 13 variants of the molecule. Next, they were tested for potency against gastric, lung, ovarian, and multidrug-resistant cancer cell lines.

“(Three of the variants showed) remarkably high potency against the tested cell lines,” the authors wrote.

The researchers noted that the analogs were stable enough to be used as payloads in antibody drug conjugates that combine a delivery system with uncialamycin by joining the 2 together through a chemical linker until they reach the target.

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