{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(4)"],"submitter":["Marcoux D"],"pubmed_abstract":["Recently, our research group reported the identification of prodrug amino-alcohol <b>2</b> as a potent and efficacious S1P<sub>1</sub> receptor modulator. This molecule is differentiated preclinically over the marketed drug fingolimod (Gilenya <b>1</b>), whose active phosphate metabolite is an S1P<sub>1</sub> full agonist, in terms of pulmonary and cardiovascular safety. S1P<sub>1</sub> partial agonist <b>2</b>, however, has a long half-life in rodents and was projected to have a long half-life in humans. The purpose of this communication is to disclose highly potent partial agonists of S1P<sub>1</sub> with shorter half-lives relative to the clinical compound <b>2</b>. PK/PD relationships as well as their preclinical pulmonary and cardiovascular safety assessment are discussed."],"journal":["MedChemComm"],"pagination":["725-729"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6071880"],"repository":["biostudies-literature"],"pubmed_title":["Identification of potent tricyclic prodrug S1P<sub>1</sub> receptor modulators."],"pmcid":["PMC6071880"],"pubmed_authors":["Marcoux D","Taylor TL","Levesque PC","Xiao HY","Murali Dhar TG","McIntyre KW","Shen DR","Wu DR","Gupta A","Cvijic ME","Cornelius G","Thomas R","Pragalathan B","Xie J","Heimrich EM","Sun H","Zhou XD","D'Arienzo CJ","Salter-Cid L","Lombardo LJ","Rampulla R","Yang X","Yang Z","Lehman-McKeeman LD","Marino AM","Carter PH","Shi H","Dabros M","Mathur A","Dyckman AJ"],"additional_accession":[]},"is_claimable":false,"name":"Identification of potent tricyclic prodrug S1P<sub>1</sub> receptor modulators.","description":"Recently, our research group reported the identification of prodrug amino-alcohol <b>2</b> as a potent and efficacious S1P<sub>1</sub> receptor modulator. This molecule is differentiated preclinically over the marketed drug fingolimod (Gilenya <b>1</b>), whose active phosphate metabolite is an S1P<sub>1</sub> full agonist, in terms of pulmonary and cardiovascular safety. S1P<sub>1</sub> partial agonist <b>2</b>, however, has a long half-life in rodents and was projected to have a long half-life in humans. The purpose of this communication is to disclose highly potent partial agonists of S1P<sub>1</sub> with shorter half-lives relative to the clinical compound <b>2</b>. PK/PD relationships as well as their preclinical pulmonary and cardiovascular safety assessment are discussed.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Apr","modification":"2025-04-19T20:59:40.523Z","creation":"2019-03-26T23:51:29Z"},"accession":"S-EPMC6071880","cross_references":{"pubmed":["30108791"],"doi":["10.1039/c6md00539j"]}}