After thirty years of research, Harvard chemists and Japanese pharmaceutical company Eisai have successfully synthesized halichondrin, an anti-cancer agent found naturally in sea sponges.
Researchers at Harvard University define their research as a “turning point in drug discovery”. In an article published in the Harvard Gazette on June 17, they describe how they managed to synthesize a molecule, halichondrin, known to be an anticancer agent. Although it is naturally present in sea sponges in very small quantities, it is such a complex molecule that it had never been created in the laboratory.
Yoshito Kishi’s team, a professor in the Harvard Department of Chemistry, specifically synthesized sufficient quantities of E7130, a “potential drug” from the halichondrin class. In preclinical studies, Japanese researchers had already identified this compound as a promising agent for targeting cancer cells. That was thirty-three years ago. It took three decades to finally produce enough.
This molecule is actually particularly difficult to manufacture because it has 31 centers of chirality, that is to say 31 points that define how it is oriented in space. According to scientists, there were therefore about “four billion ways to go wrong”. “It’s an unprecedented success […] Nobody had been able to produce halichondrin at the 10-gram level, one milligram, that’s all,” says Takashi Owa, co-author of study and responsible for the creation of drugs of the Japanese pharmaceutical company Eisai, collaborator of the project.
“Professor Kishi’s expertise has provided us with a unique and exciting opportunity to test the molecule in our systems,” he continues. He achieved a remarkable total synthesis, which allowed us to initiate a clinical trial from the E7130.”
In vitro and in vivo studies on mice have been launched to better understand its mode of action. It seems that the molecule prevents the dynamics of microtubules, important molecules for cell division. As a reminder, tumors develop as a result of disruption of cell growth.
There were already treatments that could target cancer cells, such as paclitaxel or vinblastine. But it seems that this compound is much more powerful, although it has not yet been tested on humans. The team of researchers is now hoping to begin a second clinical trial in the United States.