Helmholtz Institute for Pharmaceutical Research Saarland

Safety and pharmacokinetics of inhaled aloxistatin: A first‐in‐human phase 1 dose escalation trial

Aims Aloxistatin (E64d) is a membrane‐permeable cysteine protease inhibitor prodrug that is converted by esterases to the active metabolite E64c (loxistatin). This first‐in‐human study evaluated the safety, tolerability and pharmacokinetics of single ascending doses of inhaled E6...

DockM8: an all-in-one open-source platform for consensus virtual screening in drug design

Virtual screening remains a critical step in structure-based drug design, yet variability in docking algorithms and scoring functions often limits its reliability. To address this challenge, we introduce DockM8, an open-source platform for consensus virtual screening that integra...

Effect of Poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) Side-Chain Length on the Antimicrobial Activity of Tobramycin-POEGMA Conjugates against Pseudomonas aeruginosa

Abstract Polymer conjugation of cationic antibiotics has emerged as a promising strategy to improve their pharmacological properties and enhance their performance in biofilm-associated infections. Herein, we investigate the effect of poly[oligo(ethylene glycol) methyl ether metha...

Intermolecular Carbon–Carbon Bond Formation by a Chorismate-Converting Enzyme

Abstract Chorismate is an important precursor of many primary and secondary metabolites. Enzymes that can transform chorismate are therefore useful biocatalysts for constructing bioactive molecules, yet the scope of known chorismate biochemistry is limited. Here, we identify TunB...

Data driven selection of consensus docking pipelines for structure based hit identification

Abstract Structure-based virtual screening (SBVS) is a cornerstone of computer-aided drug design, yet its success depends on selecting a combination of docking tools, scoring function (SF), and ranking strategies. MolDockLab addresses this challenge with an automated, data-driven...

Current smoking and COPD are associated with differentiation-dependent secretory and inflammatory programs in airway basal cells

Abstract Background Persistent airway epithelial abnormalities contribute to chronic obstructive pulmonary disease (COPD), but it remains unclear whether smoking- and COPD-associated epithelial remodeling is retained in airway basal cells and transmitted during differentiation. W...

Tracheal tuft cell-released leukotrienes promote antibacterial immune responses

SUMMARY Tuft cells act as crucial sentinels in the airways that detect bacterial metabolites. In response, tuft cells release signaling molecules that trigger immune responses essential for clearing the infection. The molecular mechanisms driving immune cell activation following...

Synthesis and Activity‐Based Protein Profiling Identifies Aldo‐Keto Reductase 1C3 as Target Protein of Myxoglucamides

ABSTRACT Myxoglucamides, natural products recently isolated from Cystobacterineae sp., are featured by an unprecedented vinyl‐substituted α‐keto‐γ‐amino acid that is linked to a glycosylated 14‐methyl‐pentadecanoic acid. Thus, they unite elements from three biomolecular classes i...