A5041844615- Sphingolipid Metabolism and Signaling
- Nitric Oxide and Endothelin Effects
- Liver Disease Diagnosis and Treatment
- Proteoglycans and glycosaminoglycans research
- Cell Adhesion Molecules Research
- Cardiovascular Function and Risk Factors
- Hepatocellular Carcinoma Treatment and Prognosis
- Liver physiology and pathology
- Protein Kinase Regulation and GTPase Signaling
- Quinazolinone synthesis and applications
- Gene expression and cancer classification
- Hemostasis and retained surgical items
- Advanced Biosensing Techniques and Applications
- Circadian rhythm and melatonin
- Endoplasmic Reticulum Stress and Disease
- Apelin-related biomedical research
- Skin and Cellular Biology Research
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Ion Transport and Channel Regulation
- Platelet Disorders and Treatments
- Diet, Metabolism, and Disease
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipid Membrane Structure and Behavior
- Blood Coagulation and Thrombosis Mechanisms
Sanofi (United States)
2010-2022
Sanofi (France)
2013
University of Oxford
1996-1998
A biased S1P 1 agonist that preserves endothelial function without causing lymphopenia is identified.
Link modules are hyaluronan‐binding domains that involved in the formation and stability of extracellular matrix cell migration. We have examined glycosaminoglycan specificity module from arthritis‐associated protein, human TSG‐6, by microtitre plate‐based assays employing biotinylated‐hyaluronan or mono‐biotinylated module. This domain was found to interact specifically with chondroitin‐4‐sulphate (C4S), similar affinity hyaluronan, but not chondroitin‐6‐sulphate heparin. Competition...
Cartilage matrix is stabilised by the interactions of proteins with hyaluronan (HA). We compare pH dependences HA binding aggrecan, link protein and TSG‐6. Aggrecan exhibit maximal across a wide range (6.0–8.0). TSG‐6, that only produced during inflammation, binds maximally at about 6.0 but shows dramatic loss function increasing pH. TSG‐6 also interacts similar dependence, this can be inhibited HA. Thus, common surface on may involved in aggrecan binding. propose dissociation regulated...
Aims SAR247799 is a selective G‐protein‐biased sphingosine‐1 phosphate receptor‐1 (S1P 1 ) agonist with potential to restore endothelial function in vascular pathologies. SAR247799, first‐in‐class molecule differentiated from previous S1P ‐desensitizing molecules developed for multiple sclerosis, can activate without desensitization and consequent lymphopenia. The aim was characterize its safety, tolerability, pharmacokinetics pharmacodynamics (activation desensitization). Methods...
Aims SAR247799 is a G‐protein‐biased sphingosine‐1 phosphate receptor‐1 (S1P 1 ) agonist designed to activate endothelial S1P and provide endothelial‐protective properties, while limiting desensitization consequent lymphocyte‐count reduction associated with higher doses. The aim was show whether activation can promote effects in patients and, if so, select doses for further clinical investigation. Methods Type‐2 diabetes patients, enriched dysfunction (flow‐mediated dilation, FMD <7%; n =...
Sphingosine-1 phosphate receptor-1 (S1P
Aim Heart failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide no approved treatment. Left ventricular hypertrophy (LVH) and diastolic dysfunction represent the structural functional components HFpEF, respectively. Endothelial prevalent in HFpEF predicts cardiovascular events. We investigated if SAR247799, G-protein-biased sphingosine-1-phosphate receptor 1 (S1P ) agonist endothelial-protective properties, could improve cardiac renal functions rat model...
SAR247799 is a G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1) agonist designed to activate endothelial S1P1 and provide endothelial-protective properties, while limiting desensitization consequent lymphocyte-count reduction associated with higher doses. A dose-response study in diabetic rats 5-week treatment demonstrated, at sub-lymphocyte-reducing doses, renal function biomarker improvements was used select doses for human investigation. Type-2 diabetes patients, enriched...
Abstract Background/Introduction Heart Failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide currently no approved treatment. Diastolic dysfunction, dyspnea, intolerance to effort, high cardiac filling pressure, and lung congestion coexist normal in this clinical syndrome. Ageing, obesity, type 2 diabetes, hypertension renal dysfunction are the main comorbidities found heterogeneous group patients. Microvascular endothelial driven by these risk factors, may be...
A bstract Aim Heart failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide no approved treatment. Left ventricular hypertrophy (LVH) and diastolic dysfunction represent the structural functional components HFpEF, respectively. Endothelial prevalent in HFpEF predicts cardiovascular events. We investigated if SAR247799, G-protein-biased sphingosine-1-phosphate receptor 1 (S1P ) agonist endothelial-protective properties, could improve cardiac renal functions rat...