Meet SyntheMol — A GenAI Breakthrough in Antibiotic Resistance

Stanford Medicine and McMaster University researchers have unveiled SyntheMol, a new generative AI model designed to create chemical structures and recipes for novel drugs targeting antibiotic-resistant strains of Acinetobacter baumannii, a leading cause of antibacterial resistance-related deaths.

“There’s a huge public health need to develop new antibiotics quickly,” says James Zou, PhD, an Associate Professor of Biomedical Data Science and Co-senior Author of the study. “Our hypothesis was that there are a lot of potential molecules out there that could be effective drugs, but we haven’t made or tested them yet. That’s why we wanted to use AI to design entirely new molecules that have never been seen in nature.”

The Need for New Antibiotics

Traditional approaches to antibiotic development have limitations, prompting the exploration of AI for designing entirely new molecules with potential antibacterial properties.

SyntheMol is trained to generate potential drugs using molecular building blocks and validated chemical reactions. The model provides explicit instructions for synthesizing new compounds, ensuring feasibility for laboratory production.

Filtering and Testing

From 25,000 generated compounds, researchers identified 70 with high potential to combat resistant bacteria. Collaborating with Enamine, a chemical company, they synthesized 58 compounds, six of which exhibited effectiveness against Acinetobacter baumannii and other resistant bacteria.

Ensuring Safety

Two compounds were tested for toxicity in mice and appeared safe, warranting further investigation in live infections. These novel compounds offer promising alternatives to existing antibiotics, with potential broader implications for antibiotic development.

The synthesized compounds represent a novel area of chemical space unexplored by traditional drug discovery methods. Understanding their mechanisms of action could inform future antibiotic development strategies.

Researchers aim to refine SyntheMol for drug discovery in other areas such as heart disease and to create new fluorescent molecules for laboratory research, indicating broader applications beyond antibiotic development.