molecules of the year

June’s molecule, the BMS factor XIa inhibitor “Compound 6f”, is a potent, oral macrocyclic factor XIa inhibitor (<1 nM) that was intended as an anticoagulation agent. Since blood clotting is a significant risk for hospitalized patients that must be in a bed for days or weeks, anticoagulants are some of the most prescribed and impactful drugs in the pharmacopeia. “6f” is highly selective against other serine proteases and has excellent oral PK (high bioavailability, low clearance). Though “6f” did not progress due in part to solubility issues, the progress against a challenging target using a difficult macrocyclic scaffold is impressive.