Dataset Information

4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P1.

ABSTRACT: The sphingosine-1-phosphate-1 receptor (S1P1) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P1 agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P1 (EC50 = 0.035 ?M, 96% efficacy) and the >100-fold selectivity that it displays against receptor subtypes S1P2-5 suggest that it may serve as a valuable tool to understand the clinical relevance of selective S1P1 agonism.

SUBMITTER: Pennington LD

PROVIDER: S-EPMC4018088 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P1.

Pennington Lewis D LD Sham Kelvin K C KK Pickrell Alexander J AJ Harrington Paul E PE Frohn Michael J MJ Lanman Brian A BA Reed Anthony B AB Croghan Michael D MD Lee Matthew R MR Xu Han H McElvain Michele M Xu Yang Y Zhang Xuxia X Fiorino Michael M Horner Michelle M Morrison Henry G HG Arnett Heather A HA Fotsch Christopher C Wong Min M Cee Victor J VJ

ACS medicinal chemistry letters 20110729 10

The sphingosine-1-phosphate-1 receptor (S1P1) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P1 agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency tha ...[more]

PMID: 24900263

Dataset Information

4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P1.

Publications

4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Discovery of CS-0777: A Potent, Selective, and Orally Active S1P1 Agonist.
| S-EPMC4017972 | biostudies-other

Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone Core.
| S-EPMC4025730 | biostudies-literature

Discovery of a Potent, S1P3-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P1).
| S-EPMC4018108 | biostudies-literature

The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment.
| S-EPMC4716627 | biostudies-literature

The 2'-Trifluoromethyl Analogue of Indomethacin Is a Potent and Selective COX-2 Inhibitor.
| S-EPMC3654564 | biostudies-literature

Discovery of Clinical Candidate GSK1842799 As a Selective S1P1 Receptor Agonist (Prodrug) for Multiple Sclerosis.
| S-EPMC4027221 | biostudies-other

Discovery of a Selective S1P1 Receptor Agonist Efficacious at Low Oral Dose and Devoid of Effects on Heart Rate.
| S-EPMC4018134 | biostudies-literature

Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.
| S-EPMC4867749 | biostudies-literature

Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.
| S-EPMC129372 | biostudies-literature

Unanticipated Characteristics of a Selective, Potent Neuromedin-U Receptor 2 Agonist
| S-EPMC10125376 | biostudies-literature