Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate.

Here, we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPARα activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology suggesting therapeutic potential for NASH patients.

Bioethics and law: from the abundance of sources to the confusion of genders.

The law of bioethics reveals frequent confusion in the definition and role devolved to the law and ethics. The purpose of this paper is to illustrate some of these confusions.

Strength imbalances and prevention of hamstring injury in professional soccer players: a prospective study.

Background: The relationship between muscle injury and strength disorders remains a matter of controversy.

Purpose: Professional soccer players performed a preseason isokinetic testing aimed at determining whether (1) strength variables could be predictors of subsequent hamstring strain and (2) normalization of strength imbalances could reduce the incidence of hamstring injury.

Study Design: Cohort study (prognosis); Level of evidence, 1.

Muscular strength, functional performances and injury risk in professional and junior elite soccer players.

Muscle strength and anaerobic power of the lower extremities are neuromuscular variables that influence performance in many sports activities, including soccer. Despite frequent contradictions in the literature, it may be assumed that muscle strength and balance play a key role in targeted acute muscle injuries. The purpose of the present study was to provide and compare pre-season muscular strength and power profiles in professional and junior elite soccer players throughout the developmental years of 15-21.