Swainsonine, an alkaloid, is an inhibitor of human Golgi alpha-mannosidase II and can control cancer growth by preparing N-linked glycosylation, but clinical development has been suspended due to side effects. A team at at the Genomic Research Center of Academia Sinica in Taiwan has designed a hybrid skeleton that combines the structures of the pyrrolidine-based alkaloid AN9 and the bicyclic alkaloid swainsonine to generate a candidate skeleton. Using a technique called “natural product-inspired combinatorial chemistry,” the team rapidly generated a library of indolizidine-based molecules. Using this library, the team screened for a compound, ACK900, which is an effective and selective inhibitor of α-hGMII. Animal studies showed that this compound is a promising anticancer drug candidate.
Academica Sinica Taiwan detects new lead for anti-cancer drug