Endothelial‐protective effects of a G‐protein‐biased sphingosine‐1 phosphate receptor‐1 agonist, SAR247799, in type‐2 diabetes rats and a randomized placebo‐controlled patient trial

Autor: Theresa Herbrand, Bruno Poirier, Philip Janiak, Anthony J. Muslin, Paul Deutsch, Hans Veit Coester, Xavier Benain, Lionel Hovsepian, Luc Bergougnan, Maria Francesca Evaristi, Ashfaq Parkar, Jorge Arrubla, Rania Boiron, Grit Andersen, Olivier Vitse, Agnes Tardat, Roberto Sansone, Stephane Kirkesseli, Christian Heiss, Radzik Davide, Leona Plum-Mörschel, Marcel Ermer, Fabrice Hurbin
Rok vydání: 2020
Předmět:
Agonist
medicine.medical_specialty
Brachial Artery
endothelium
Endothelium
medicine.drug_class
Sildenafil
medicine.medical_treatment
Sphingosine-1-phosphate receptor
Renal function
SAR247799
Type 2 diabetes
Pharmacology
flow‐mediated dilation
Placebo
030226 pharmacology & pharmacy
Gastroenterology
Phosphates
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
GTP-Binding Proteins
Sphingosine
Internal medicine
Diabetes mellitus
medicine
Animals
Humans
Pharmacology (medical)
030212 general & internal medicine
Endothelial dysfunction
Desensitization (medicine)
sphingosine‐1 phosphate receptor‐1
diabetes
business.industry
Original Articles
medicine.disease
Rats
Rats
Zucker
Vasodilation
Blood pressure
medicine.anatomical_structure
Diabetes Mellitus
Type 2
chemistry
Original Article
Endothelium
Vascular
business
Zdroj: British Journal of Clinical Pharmacology
ISSN: 1365-2125
0306-5251
DOI: 10.1111/bcp.14632
Popis: AIMS 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 S1P1 desensitization and consequent lymphocyte-count reduction associated with higher doses. The aim was to show whether S1P1 activation can promote endothelial effects in patients and, if so, select SAR247799 doses for further clinical investigation. METHODS Type-2 diabetes patients, enriched for endothelial dysfunction (flow-mediated dilation, FMD
Databáze: OpenAIRE
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