PRN301

PRN301 is a small molecule, reversible covalent inhibitor of Bruton's tyrosine kinase (BTK) that was developed for the treatment of immune-mediated diseases. Developed by Principia Biopharma (now a subsidiary of Sanofi), the compound utilizes a proprietary cyanoacrylamide-based chemistry to form a reversible covalent bond with a specific cysteine residue (Cys481) in the BTK protein. This mechanism is designed to provide the prolonged target occupancy characteristic of irreversible inhibitors while potentially offering a better safety profile by allowing the drug to dissociate from the target over time. Although initially part of Principia's pipeline for inflammatory conditions, the program appears to have been superseded by other BTK inhibitors in the company's portfolio, such as rilzabrutinib (PRN1008) and tolebrutinib (PRN2246), and is no longer listed in active clinical development.