Discovery of a Potent, Selective, and Orally Bioavailable Tool Compound for Probing the Role of Lysophosphatidic Acid Type 2 Receptor Antagonists in Fibrotic Disorders.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by lung fibrosis leading to an irreversible decline of lung function. Current antifibrotic drugs on the market slow down but do not prevent the progression of the disease and are associated with tolerability issues. The involvement of lysophosphatidic acid receptor 2 (LPA) in IPF is supported by LPA knockdown studies.

Duodenojejunal inflammation causing chronic vomiting in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease with a broad spectrum of clinical manifestations including fever, skin rash, arthralgia and neutrophilic leucocytosis. Small bowel inflammation in AOSD has been reported in association with Crohn's disease, coeliac disease and chronic intestinal pseudo-obstruction. We have here reported the first-time case of AOSD with small bowel involvement, presenting with chronic vomiting.

Discovery of Clinical Candidate CHF-6366: A Novel Super-soft Dual Pharmacology Muscarinic Antagonist and β Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases.

The development of molecules embedding two distinct pharmacophores acting as muscarinic antagonists and β agonists (MABAs) promises to be an excellent opportunity to reduce formulation issues and boost efficacy through cross-talk and allosteric interactions. Herein, we report the results of our drug discovery campaign aimed at improving the therapeutic index of a previous MABA series by exploiting the super soft-drug concept. The incorporation of a metabolic liability, stable at the site of administration but undergoing rapid systemic metabolism, to generate poorly active and quickly eliminated fragments was pursued.

Hyaluronic Acid Therapy in Hip OA Does Not Perform Equally in Osteoarthritis Secondary to Juvenile Idiopathic Arthritis When Compared to Primary Osteoarthritis: A 2-Year Preliminary Evaluation.

Objective: Hip involvement in juvenile idiopathic arthritis (JIA) is one of most important causes of pain and disability. Total hip arthroplasty (THA) is considered the standard when medical approaches fail to relieve pain. However, THA is problematic for many reasons.