Sphingosine 1-phosphate receptor 1 agonists: a patent review (2013-2015)

@article{Guerrero2016Sphingosine1R,
  title={Sphingosine 1-phosphate receptor 1 agonists: a patent review (2013-2015)},
  author={M. Guerrero and M. Urbano and E. Roberts},
  journal={Expert Opinion on Therapeutic Patents},
  year={2016},
  volume={26},
  pages={455 - 470}
}
ABSTRACT Introduction: The sphingosine-1-phosphate (S1P) regulates diverse biological functions including cell proliferation, endothelial cell chemotaxis, angiogenesis, immune cell trafficking, mitogenesis, heart rate. The first-in-class S1P1,3–5-R pan-agonist fingolimod (FTY720) was approved by the FDA and EMEA for the treatment of relapsing-remitting multiple sclerosis, though the most common adverse effect is bradycardia which occurs in the early stage of treatment and resolves within the… Expand
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References

SHOWING 1-10 OF 96 REFERENCES
Modulators of the Sphingosine 1-phosphate receptor 1.
TLDR
This review provides the latest advances on next-generation S1P1-R modulators from 2012 up to date, with an overview of the chemical structures, structure-activity relationships, and relevant biological and clinical properties. Expand
S1P signaling: new therapies and opportunities
TLDR
Proof-of-concept studies across validated animal models with S1P receptor modulators highly selective for S 1P1, and emerging clinical trials for safety and efficacy in humans, particularly in MS, ulcerative colitis (UC) and psoriasis, have set the stage for the company to consider additional testing in various other autoimmune diseases. Expand
Sphingosine 1-phosphate receptor signaling.
TLDR
The sphingosine 1-phosphate (S1P) receptor signaling system, based in part on receptor subtype-selectivity and on differential attenuation of deleterious signals, now appears to be on the cusp of meaningful therapy for multiple sclerosis. Expand
The alliance of sphingosine-1-phosphate and its receptors in immunity
TLDR
Findings indicate that the alliance between S1P and its receptors has a fundamental role in immunity, and the discovery of regulatory mechanisms in S1p-mediated immune-cell trafficking and new advances in understanding the mechanism by which S 1P affects immune- cell function indicate that this alliance is important for immunity. Expand
Sphingosine 1-Phosphate (S1P) Regulates Vascular Contraction via S1P3 Receptor: Investigation Based on a New S1P3 Receptor Antagonist
TLDR
The results clearly show that TY-52156 is both sensitive and useful as an S1P3 receptor-specific antagonist and reveal that S 1P induces vasoconstriction by directly activating S1p3 receptor and through a subsequent increase in [Ca2+]i and Rho activation in vascular smooth muscle cells. Expand
Sphingosine 1-Phosphate (S1P) Receptor Subtypes S1P1 and S1P3, Respectively, Regulate Lymphocyte Recirculation and Heart Rate*
TLDR
S 1P1-selective agonists will be of broad utility in understanding cell functions in vitro, and vascular physiology in vivo, and the success of the chemical approach for S1P1 suggests that selective tools for the resolution of function across this broad lipid receptor family are now possible. Expand
Prolonged exposure to sphingosine 1-phosphate receptor-1 agonists exacerbates vascular leak, fibrosis, and mortality after lung injury.
TLDR
It is demonstrated that repeated administration of S1P(1) agonists dramatically worsened lung injury after bleomycin challenge, as manifested by increased vascular leak and mortality and the hypothesis that vascular leak is an important component of the fibrogenic response to lung injury is supported. Expand
Phytosphingosine 1-phosphate: a high affinity ligand for the S1P(4)/Edg-6 receptor.
TLDR
The present study demonstrates the utility of a novel radiolabeled probe, PhS133P, for in vitro studies of the S1P(4) receptor pharmacology, and proves to be superior to S133P in routine binding assays due to improved signal-to-noise ratio. Expand
The Clinically-tested S1P Receptor Agonists, FTY720 and BAF312, Demonstrate Subtype-Specific Bradycardia (S1P1) and Hypertension (S1P3) in Rat
TLDR
In vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1p1 receptors mediate bradycardia while hypertension is mediated by S1 P3 receptor activation. Expand
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate
TLDR
The immunomodulatory potential of BAF312 and the S1P receptor‐mediated effects on heart rate are characterized using preclinical and human data. Expand
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