Insilico Medicine, a pioneering company in generative artificial intelligence (AI)-driven drug discovery, has recently made a groundbreaking discovery in the field of medicinal chemistry. Using their proprietary AI platform, Chemistry42, researchers at Insilico have identified a new class of inhibitors targeting DNA Polymerase Theta (Polθ), a crucial player in genomic integrity maintenance.
The newly discovered Polθ inhibitors show strong potency and promising drug-like properties, offering a potential treatment strategy for BRCA-deficient tumors, which are prevalent in certain types of cancers such as triple-negative breast cancers (TNBC) and ovarian cancers. With limited treatment options and increasing resistance issues, the development of alternative therapies like Polθ inhibitors is essential.
Through a combination of ligand-based and structure-based drug design strategies, the Insilico team was able to identify a novel lead compound with central scaffold rings. Further optimization led to the development of 3-hydroxymethyl-azetidine derivatives, a novel class of Polθ inhibitors with significant enzymatic and cellular potency.
In subsequent validation studies, one of the newly developed compounds demonstrated robust cellular potency in DNA repair-compromised cells, along with favorable pharmacokinetic properties in vivo. This orally bioavailable molecule holds promise as a potential treatment for solid cancers with BRCA1/2 mutations, showcasing the potential of AI in medicinal chemistry for precise molecular modifications.
Insilico Medicine’s innovative approach to drug discovery has led to advancements in various disease areas, including fibrosis, cancer, immunology, and aging-related diseases. With a portfolio of over 30 assets and several pipelines in the clinical stage, Insilico continues to push the boundaries of AI-driven drug development.
The recent findings published in Bioorganic & Medicinal Chemistry underscore the power of AI in accelerating the discovery and development of novel therapies. By leveraging the capabilities of generative AI, Insilico Medicine is at the forefront of revolutionizing the pharmaceutical industry and bringing innovative treatments to patients worldwide.
