LTA4H inhibitor LYS006: Clinical PK/PD and safety in a randomized phase I clinical trial.

LYS006 is a novel, highly potent and selective, new-generation leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophil-driven inflammatory diseases. We describe the complex pharmacokinetic to pharmacodynamic (PD) relationship in blood, plasma, and skin of LYS006-treated nonclinical species and healthy human participants. In a randomized first in human study, participants were exposed to single ascending doses up to 100 mg and multiple ascending doses up to 80 mg b.

A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism-A Proof-of-Concept Trial.

Context: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation.

Objective: Evaluate efficacy and safety of a human, blocking, nondepleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD.

Design: Open-label, phase II proof-of-concept study.

Marine Bacteria, XLVII - Psychrotolerant Bacteria from Extreme Antarctic Habitats as Producers of Rare Bis- and Trisindole Alkaloids.

From the gastrointestinal tract of a fish dredged near the South Orkney Islands in Antarctica, we isolated the psychrotolerant bacterial strain T262, which belongs to the species Vibrio splendidus. Investigation of this strain led to the isolation of a series of 15 bis- and trisindole derivatives. Among them, six new indole alkaloids, namely, turbomycin C [4'-n-butoxyphenyl-bis(1H-indol-3-yl)methane, 1a], turbomycin D [4'-n-propoxyphenyl-bis(1H-indol-3-yl)methane, 1b], turbomycin E [4'-ethoxyphenyl-bis(1H-indol-3-yl)methane, 1c], turbomycin F [4'-methoxy-3',5'-dinitrophenyl-bis(1H-indol-3-yl)methane, 2], trisindolal (3a), and 4-(1H-indol-3-yl-sulfanyl)phenol (4).

Nitro derivatives from the Arctic ice bacterium Salegentibacter sp. isolate T436.

Twenty-five aromatic nitro, dinitro and trinitro compounds were isolated in low yields of less than 1 mg l(-1) from a Salegentibacter sp. strain T436 derived from Arctic pack ice. Their structures were elucidated by MS and NMR techniques.

New aromatic nitro compounds from Salegentibacter sp. T436, an Arctic Sea ice bacterium: taxonomy, fermentation, isolation and biological activities.

Nineteen aromatic nitro compounds were isolated from the culture broth of an Arctic sea ice bacterium. Four of these compounds are new and six compounds are reported from a natural source for the first time. The new natural products showed weak antimicrobial and cytotoxic activities.