Discovery of BAY 3389934 Hydrochloride: A Potent and Selective Small-Molecule Dual Factor IIa/Xa Inhibitor with Short Half-Life for the Acute Treatment of Sepsis-Induced Coagulopathy
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Sepsis-induced coagulopathy (SIC) is a severe and frequent complication of sepsis, which is associated with high mortality in patients. So far, attempts have failed to establish a global standard of care in this difficult-to-treat indication. Anticoagulation with a dual inhibitor of the coagulation factors IIa (FIIa, thrombin) and Xa (FXa) has the potential to improve the treatment of life-threatening acute coagulation disorders, such as SIC. Herein, we describe the discovery of BAY 3389934 hydrochloride ( 31 ), a potent and highly selective, direct dual FIIa/Xa inhibitor, with high solubility suited for i.v. application. This small molecule acts as a metabolically soft active pharmaceutical ingredient (API) due to a labile carboxylic ester group, which is responsible for the desired short pharmacokinetic and pharmacological half-life ( t 1/2 ), resulting in a high controllability of the pharmacological action.
Source: Journal of Medicinal Chemistry
Authors: Hartmut Beck, Stefanie Mesch, Stefanie Zimmermann, Alexandros Vakalopoulos, Lutz Lehmann, Kersten Matthias Gericke, Frank Süßmeier, Lars Baerfacker, Alexander Hillisch, Katharina Meier, Adrian Tersteegen, Anja Buchmüller, Christoph Gerdes, Julia Dietze-Torres, Elisabeth Kersten, Katrin Partikel, Andreas Bröhl, Guillaume Levilain, Stefan Heitmeier, Nils Pfaff, Markus Follmann
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4411205834