Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDZCKV)

• DTT Name: Sphingosine-1-phosphate receptor 5 (S1PR5)
• Synonyms: Sphingosine 1-phosphate receptor Edg-8; S1PR5; S1P5; S1P receptor Edg-8; S1P receptor 5; Endothelial differentiation G-protein-coupled receptor 8
• Gene Name: S1PR5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: S1PR5_HUMAN
• TTD ID: T50089
• Sequence:
  MESGLLRPAPVSEVIVLHYNYTGKLRGARYQPGAGLRADAVVCLAVCAFIVLENLAVLLV
  LGRHPRFHAPMFLLLGSLTLSDLLAGAAYAANILLSGPLTLKLSPALWFAREGGVFVALT
  ASVLSLLAIALERSLTMARRGPAPVSSRGRTLAMAAAAWGVSLLLGLLPALGWNCLGRLD
  ACSTVLPLYAKAYVLFCVLAFVGILAAICALYARIYCQVRANARRLPARPGTAGTTSTRA
  RRKPRSLALLRTLSVVLLAFVACWGPLFLLLLLDVACPARTCPVLLQADPFLGLAMANSL
  LNPIIYTLTNRDLRHALLRLVCCGRHSCGRDPSGSQQSASAAEASGGLRRCLPPGLDGSF
  SGSERSSPQRDGLDTSGSTGSPGAPTAARTLVSEPAAD
• Function: Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins. May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells.
• KEGG Pathway:
  Sphingolipid signaling pathway (hsa04071)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  Lysosphingolipid and LPA receptors (R-HSA-419408)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP-4058	DM1RD0T	Multiple sclerosis	8A40	Phase 1	[1]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AFD(R)	DME9Y8Q	Discovery agent	N.A.	Investigative	[2]
AUY954	DMVGIO5	Discovery agent	N.A.	Investigative	[3]
FTY720-phosphate	DMDZBQH	Discovery agent	N.A.	Investigative	[4]
VPC03090-P	DMIXUM3	Discovery agent	N.A.	Investigative	[5]
VPC44116	DMQ4OTJ	Discovery agent	N.A.	Investigative	[6]

References

• [1] ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS One. 2014 Oct 27;9(10):e110819.
• [2] Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004 Apr 2;279(14):13839-48.
• [3] A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol. 2006 Nov;13(11):1227-34.
• [4] Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004 May;309(2):758-68.
• [5] Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J Pharmacol Exp Ther. 2011 Sep;338(3):879-89.
• [6] Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg Med Chem. 2007 Jan 15;15(2):663-77.