Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution.

Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524).

Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12.

A subset of phosphodiesterase 3 (PDE3) inhibitors kills cancer cells that express both PDE3A and SLFN12 by inducing a protein-protein interaction between the two, triggering SLFN12 tRNase activity. Following discovery of the prototypical tool compound, , an improved compound, , was discovered to be potent in cells and active in several tumor models . More analogs were prepared and tested with the goal of increasing metabolic stability and decreasing PDE3 inhibition while maintaining the cellular activity of .

Prevention of legionella infections from toilet flushing cisterns.

Introduction: Immunocompromised patients are at an increased risk of severe legionella infections. We present the results of an outbreak investigation initiated following a fatal case of hospital-acquired legionellosis linked to contaminated water from a toilet-flushing cistern. Additionally, we provide experimental data on the growth of Legionella spp.

a new member of the Yersineacea family has the characteristics of a human pathogen.

(heterotypic synonym: "") is a facultative anaerobic, newly described Gram-negative rod and belongs to the Yersineacea family. Here, we report the case of a 19-month-old female infant patient who presented to the emergency unit with somnolence and fever. was isolated from a positive blood culture, taken via an implanted Broviac catheter, proving a bloodstream infection by the pathogen.

Design and Preclinical Characterization Program toward Asundexian (BAY 2433334), an Oral Factor XIa Inhibitor for the Prevention and Treatment of Thromboembolic Disorders.

Activated coagulation factor XI (FXIa) is a highly attractive antithrombotic target as it contributes to the development and progression of thrombosis but is thought to play only a minor role in hemostasis so that its inhibition may allow for decoupling of antithrombotic efficacy and bleeding time prolongation. Herein, we report our major efforts to identify an orally bioavailable, reversible FXIa inhibitor. Using a protein structure-based design approach, we identified a novel micromolar hit with attractive physicochemical properties.