Covalent drugs just got a new ‘spring-loaded’ warhead
Sulfur(IV) reagent allows late-stage installation of bicyclobutanes to drug molecules, expanding a limited tool box
The tool-kit for covalent drugs has been expanded with a new class of molecular warhead that relies on the ‘spring-loaded’ reactivity of bicyclobutanes. The researchers suggest that the approach could lead to safer therapeutics with fewer side-effects for patients and potentially expand the spectrum of diseases that can be treated with covalent drugs.
Covalent drugs have a functional group, or warhead, that forms a covalent bond with an amino acid on a target protein, usually to inhibit an enzyme. Toxicity concerns traditionally hindered their development but recent years have seen these obstacles overcome with several covalent drugs now approved for the clinic.