Target family: Lysophospholipid (S1P) receptors (type: gpcr)
Target: S1P<sub>5</sub> receptor

Ligand: VPC44116 (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 7.5 pEC50
Reference (Journal): Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists.
Published in: Bioorg Med Chem

Ligand: VPC03090-P (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity: 8.640000343322754 pKd
Reference (Journal): Characterization of a sphingosine 1-phosphate receptor antagonist prodrug.
Published in: J Pharmacol Exp Ther

Ligand: VPC03090-P (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Primary target: no
Median affinity: 8.619999885559082 pEC50
Reference (Journal): Characterization of a sphingosine 1-phosphate receptor antagonist prodrug.
Published in: J Pharmacol Exp Ther

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.
Published in: J Biol Chem

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Median affinity: 8.7 pKd
Reference (Journal): Characterization of a novel sphingosine 1-phosphate receptor, Edg-8.
Published in: J Biol Chem

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): The immune modulator FTY720 targets sphingosine 1-phosphate receptors.
Published in: J Biol Chem

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model.
Published in: Chem Biol

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.
Published in: J Biol Chem

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors.
Published in: Biochemistry

Ligand: sphingosine 1-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors.
Published in: Biochemistry

Ligand: siponimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2019), EMA (2020)
Primary target: yes
Median affinity: 9.010000228881836 pEC50
Reference (Journal): The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Published in: Br J Pharmacol

Ligand: siponimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2019), EMA (2020)
Primary target: yes
Median affinity: 9.010000228881836 pEC50
Reference (Journal): Modulators of the Sphingosine 1-phosphate receptor 1.
Published in: Bioorg Med Chem Lett

Ligand: siponimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2019), EMA (2020)
Primary target: yes
Median affinity: 9.010000228881836 pEC50
Reference (Journal): A complement to care.
Published in: Nurs Times

Ligand: RP-101075 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: yes
Median affinity: 8.229999542236328 pEC50
Reference (Journal): Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus.
Published in: PLoS ONE

Ligand: ponesimod (Synthetic organic)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: yes
Approval source: EMA & FDA (2021)
Primary target: yes
Median affinity: 6.849999904632568 pIC50
Reference (Journal): 2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.
Published in: J Med Chem

Ligand: ozanimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: EMA & FDA (2020)
Primary target: yes
Median affinity: 7.960000038146973 pEC50
Reference (Journal): Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.
Published in: Br J Pharmacol

Ligand: ozanimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: EMA & FDA (2020)
Primary target: no
Median affinity: 7.260000228881836 pEC50
Reference (Patent): Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis.

Ligand: GSK2018682 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 7.199999809265137 pEC50
Reference (Journal): Safety, pharmacokinetics, pharmacodynamics, and bioavailability of GSK2018682, a sphingosine-1-phosphate receptor modulator, in healthy volunteers.
Published in: Clin Pharmacol Drug Dev

Ligand: fingolimod-phosphate (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model.
Published in: Chem Biol

Ligand: fingolimod-phosphate (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): The immune modulator FTY720 targets sphingosine 1-phosphate receptors.
Published in: J Biol Chem

Ligand: fingolimod-phosphate (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 9.220000267028809 pIC50
Reference (Journal): Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: fingolimod-phosphate (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes.
Published in: J Pharmacol Exp Ther

Ligand: fingolimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2010), EMA (2011)
Primary target: yes
Median affinity: 5.679999828338623 pIC50
Reference (Journal): A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists.
Published in: J Med Chem

Ligand: etrasimod (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2023)
Primary target: no
Median affinity: 7.610000133514404 pEC50
Reference (Journal): Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.
Published in: ACS Med Chem Lett

Ligand: compound 43 [PMID: 26751273] (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 7.78000020980835 pEC50
Reference (Journal): Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses.
Published in: J Med Chem

Ligand: compound 26 [PMID: 16190743] (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Median affinity: 9 pIC50
Reference (Journal): Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.
Published in: J Med Chem

Ligand: compound 15 [PMID: 33738061] (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 10 pIC50
Reference (Journal): Novel Potent Selective Orally Active S1P5 Receptor Antagonists.
Published in: ACS Med Chem Lett

Ligand: AUY954 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Median affinity: 6.5 pEC50
Reference (Journal): A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model.
Published in: Chem Biol

Ligand: AUY954 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 6.46999979019165 pEC50
Reference (Journal): A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model.
Published in: Chem Biol

Ligand: ASP4058 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: yes
Median affinity: 8.119999885559082 pEC50
Reference (Journal): ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile.
Published in: PLoS ONE

Ligand: AFD(R) (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.
Published in: J Biol Chem

Ligand: AFD(R) (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): The immune modulator FTY720 targets sphingosine 1-phosphate receptors.
Published in: J Biol Chem

Ligand: A-971432 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: yes
Median affinity: 8.239999771118164 pEC50
Reference (Journal): Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders.
Published in: J Med Chem

Ligand: A-971432 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: yes
Median affinity: 8.390000343322754 pEC50
Reference (Journal): Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders.
Published in: J Med Chem

Ligand: A-971432 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: yes
Median affinity: 8.239999771118164 pEC50
Reference (Journal): Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease.
Published in: Hum Mol Genet