Discovery of Clinical Candidate GLPG3970: A Potent and Selective Dual SIK2/SIK3 Inhibitor for the Treatment of Autoimmune and Inflammatory Diseases.

The salt-inducible kinases (SIKs) SIK1, SIK2, and SIK3 belong to the adenosine monophosphate-activated protein kinase (AMPK) family of serine/threonine kinases. SIK inhibition represents a new therapeutic approach modulating pro-inflammatory and immunoregulatory pathways that holds potential for the treatment of inflammatory diseases. Here, we describe the identification of GLPG3970 (), a first-in-class dual SIK2/SIK3 inhibitor with selectivity against SIK1 (IC of 282.

A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA).

MurA (UDP-N-acetylglucosamine enolpyruvyl transferase, EC 2.5.1.

In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor.

Objectives: Production of beta-lactamases is the main mechanism of beta-lactam resistance in Gram-negative bacteria. Despite the current use of clavulanic acid, sulbactam and tazobactam, the prevalence of class A and class C enzymes is increasing worldwide, demanding new beta-lactamase inhibitors. Here we report the antimicrobial properties of AVE1330A, a representative of a novel class of bridged bicyclico[3.