S1PR5

Summary

S1PR5 (sphingosine-1-phosphate receptor 5, HGNC:14299) is a protein-coding gene on chromosome 19p13.2, encoding Sphingosine 1-phosphate receptor 5 (Q9H228). Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P).

The lysosphingolipid sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Its actions may be both intracellular as a second messenger and extracellular as a receptor ligand. S1P and the structurally related lysolipid mediator lysophosphatidic acid (LPA) signal cells through a set of G protein-coupled receptors known as EDG receptors. Some EDG receptors (e.g., EDG1; MIM 601974) are S1P receptors; others (e.g., EDG2; MIM 602282) are LPA receptors.

Source: NCBI Gene 53637 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14299
Approved symbol	S1PR5
Name	sphingosine-1-phosphate receptor 5
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Edg-8
Ensembl gene	ENSG00000180739
Ensembl biotype	protein_coding
OMIM	605146
Entrez	53637

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000333430, ENST00000439028, ENST00000590601

RefSeq mRNA: 2 — MANE Select: NM_030760 NM_001166215, NM_030760

CCDS: CCDS12240

Canonical transcript exons

ENST00000333430 — 2 exons

Exon	Start	End
ENSE00001516064	10517398	10517447
ENSE00003715487	10512742	10515029

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 97.55.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5473 / max 439.5996, expressed in 653 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179149	3.6021	495
179150	0.4877	265
179148	0.4575	142

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.55	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.86	gold quality
spinal cord	UBERON:0002240	92.83	gold quality
medial globus pallidus	UBERON:0002477	92.11	gold quality
inferior vagus X ganglion	UBERON:0005363	90.50	gold quality
globus pallidus	UBERON:0001875	90.01	gold quality
corpus callosum	UBERON:0002336	89.26	gold quality
substantia nigra	UBERON:0002038	88.64	gold quality
midbrain	UBERON:0001891	88.01	gold quality
upper arm skin	UBERON:0004263	87.54	silver quality
subthalamic nucleus	UBERON:0001906	85.19	gold quality
blood	UBERON:0000178	85.07	gold quality
putamen	UBERON:0001874	84.86	gold quality
lower esophagus mucosa	UBERON:0035834	84.50	gold quality
Ammon’s horn	UBERON:0001954	83.16	gold quality
amygdala	UBERON:0001876	83.04	gold quality
ventral tegmental area	UBERON:0002691	82.03	gold quality
skin of abdomen	UBERON:0001416	81.87	gold quality
dorsal plus ventral thalamus	UBERON:0001897	81.78	gold quality
hypothalamus	UBERON:0001898	81.03	gold quality
esophagus squamous epithelium	UBERON:0006920	80.93	gold quality
esophagus mucosa	UBERON:0002469	80.17	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.09	gold quality
gingival epithelium	UBERON:0001949	80.05	gold quality
zone of skin	UBERON:0000014	79.85	gold quality
skin of hip	UBERON:0001554	79.60	gold quality
gingiva	UBERON:0001828	79.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.47	gold quality
superior vestibular nucleus	UBERON:0007227	79.43	gold quality
skin of leg	UBERON:0001511	79.27	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	91.45
E-CURD-122	yes	50.47
E-MTAB-9467	yes	38.11
E-MTAB-6701	yes	33.01
E-MTAB-6678	yes	12.33
E-ANND-3	yes	11.29
E-GEOD-106540	no	556.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting S1PR5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-647	97.73	67.79	927
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-6736-3P	96.98	65.22	1342

Literature-anchored findings (GeneRIF, showing 15)

• The molecular identity, functional properties, and expression profile of the S1P5 (Edg-8) receptor have been characterized. (PMID:11705398)
• differences between hS1P(5) and rS1P(5) will be an important point to be considered in the development of selective receptor antagonists. (PMID:12234605)
• identify and characterize the gene; describe its expression in normal tissues and large granular lymphocyte leukemia monocytes (PMID:12427546)
• FTY720 induces time-dependent modulation of S1P receptors on human OPCs with consequent functional responses that are directly relevant for the remyelination process. (PMID:17918267)
• The centrosomal sphingosine-1-phosphate receptor 5 might function as an intracellular target of sphingosine-1-phosphate linked to regulation of mitosis. (PMID:19211033)
• Results suggest that, under serum-starved conditions, sphingosine 1-phosphate (S1P) further upregulates autophagic activity through S1P(5)-dependent pathways in PC-3 cells. (PMID:19474291)
• The decreased expression level of S1PR5 on NK cells is associated with graft versus host disease occurrence after allogeneic hematopoietic stem cell transplantation. (PMID:22541110)
• Edg-5 receptor in brain endothelial cells contributes to optimal barrier formation and maintenance of immune quiescence of the barrier endothelium. (PMID:22715976)
• This report is the first to demonstrate a reduction in S1P5 in multiple sclerosis lesions, which parallels that of myelin loss. (PMID:23551178)
• Data show that sphingosine kinase SphK1 and sphingosine-1-phosphate (S1P) receptors S1P1, S1P2, S1P3, and S1P5 were expressed from primary, up to recurrent and secondary glioblastomas, with sphingosine kinase SphK2 levels were highest in primary tumors. (PMID:24903384)
• TGF-beta2 dependent upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF-beta in mesangial cells. (PMID:25601519)
• Reduced DNA methylation may underlie the increased expression of the S1PR5 gene in alveolar macrophages and associated defective efferocytosis in COPD. (PMID:27868302)
• Data indicate that the mitotic kinase Polo-like kinase 1 (PLK1) was an important effector of S1P-S1P5 signaling, and a new function of the SphK1-S1P pathway specifically in the control of mitosis in HeLa cells. (PMID:28351953)
• our findings establish that S1PR5 is of central importance for human NK-cell response to sphingosine-1-phosphate and suggest that it is required for their egress from the bone marrow and secondary lymphoid organs. (PMID:29248494)
• Interactions between lysophosphatidylinositol receptor GPR55 and sphingosine-1-phosphate receptor S1P5 in live cells. (PMID:34271437)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	s1pr5a	ENSDARG00000040526
danio_rerio	s1pr5b	ENSDARG00000052192
mus_musculus	S1pr5	ENSMUSG00000045087
rattus_norvegicus	S1pr5	ENSRNOG00000020901

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Sphingosine 1-phosphate receptor 5 — Q9H228 (reviewed: Q9H228)

Alternative names: Endothelial differentiation G-protein-coupled receptor 8, Sphingosine 1-phosphate receptor Edg-8

All UniProt accessions (2): Q9H228, K7EIT5

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed in the brain, most prominently in the corpus callosum, which is predominantly white matter. Detected in spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal spleen. Low-level signal detected in many tissue extracts. Overexpressed in leukemic large granular lymphocytes. Isoform 1 is predominantly expressed in peripheral tissues. Isoform 2 is expressed in brain, spleen and peripheral blood leukocytes.

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H228-1	1	yes
Q9H228-2	2

RefSeq proteins (2): NP_001159687, NP_110387* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004061	S1P_rcpt	Family
IPR005386	EDG8_S1P_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (42 total): helix 14, topological domain 8, transmembrane region 7, strand 3, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1, glycosylation site 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7YXA	X-RAY DIFFRACTION	2.2
7EW1	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H228-F1	78.37	0.49

Antibody-complex structures (SAbDab): 1 — 7EW1

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 381, 323

Glycosylation sites (1): 20

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-419408	Lysosphingolipid and LPA receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 153 (showing top): GOBP_SPHINGOLIPID_MEDIATED_SIGNALING_PATHWAY, SP1_Q2_01, CEBPB_01, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, RICKMAN_METASTASIS_DN, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GNF2_IL2RB, AFFAR_YY1_TARGETS_UP, MAYBURD_RESPONSE_TO_L663536_DN, PID_S1P_META_PATHWAY, MODULE_48, MODULE_95, GNF2_PTPN4, LEIN_OLIGODENDROCYTE_MARKERS, GOCC_SYNAPSE

GO Biological Process (4): adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), sphingosine-1-phosphate receptor activity (GO:0038036), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), presynapse (GO:0098793), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
G protein-coupled receptor signaling pathway	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
sphingolipid mediated signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
transmembrane signaling receptor activity	1
sphingosine-1-phosphate receptor signaling pathway	1
bioactive lipid receptor activity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
synapse	1

Protein interactions and networks

STRING

912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S1PR5	SPHK1	Q9NYA1	936
S1PR5	GNA12	Q03113	905
S1PR5	SPHK2	Q9NRA0	898
S1PR5	LPAR4	Q99677	650
S1PR5	SPNS2	Q8IVW8	629
S1PR5	ARRB1	P49407	608
S1PR5	GNAQ	P50148	607
S1PR5	MFSD2B	A6NFX1	603
S1PR5	CXCR4	P30991	587
S1PR5	ARRB2	P32121	569
S1PR5	SMPD1	P17405	550
S1PR5	CXCL12	P48061	550
S1PR5	SGPL1	O95470	520
S1PR5	KLRD1	Q13241	510
S1PR5	APOM	O95445	491

IntAct

21 interactions, top by confidence:

A	B	Type	Score
S1PR5	GJA8	psi-mi:“MI:0915”(physical association)	0.560
GJA8	S1PR5	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	S1PR5	psi-mi:“MI:0915”(physical association)	0.560
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
S1PR5	CCR2	psi-mi:“MI:0915”(physical association)	0.370
S1PR5	SMO	psi-mi:“MI:0915”(physical association)	0.370
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
VNN2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
TP63	HNRNPR	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
KLRC2	CLGN	psi-mi:“MI:0914”(association)	0.350
S1PR5	SSMEM1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): S1PR5 (Affinity Capture-MS), S1PR5 (Affinity Capture-MS), S1PR5 (Affinity Capture-MS), S1PR5 (Affinity Capture-MS), S1PR5 (Affinity Capture-MS), S1PR5 (Affinity Capture-MS), S1PR5 (Two-hybrid), S1PR5 (Two-hybrid), S1PR5 (Affinity Capture-MS), S1PR5 (Two-hybrid), S1PR5 (Two-hybrid), S1PR5 (Affinity Capture-MS), S1PR5 (Affinity Capture-RNA), S1PR5 (Affinity Capture-RNA), S1PR5 (Affinity Capture-MS)

ESM2 similar proteins: A6NGC4, A6NKX4, A6NM10, D3YZZ2, O35595, O46547, O60391, O77808, O95528, P30518, P43119, P46092, P46095, P48044, P48748, Q14626, Q3SYU3, Q3ZAV1, Q4U2R8, Q4W8A3, Q5RF19, Q5U419, Q64385, Q684M3, Q6UXD7, Q6UXT9, Q6YNI2, Q863Y8, Q86SM5, Q8CFZ5, Q8IXF9, Q8WUG5, Q91X56, Q924U0, Q96S37, Q99MF4, Q9BGL8, Q9BZ11, Q9H1Z9, Q9H228

Diamond homologs: O02777, O08530, O77408, O77621, O95136, P20272, P21453, P21554, P30546, P30966, P31389, P31390, P34972, P35367, P47746, P47752, P47936, P48303, P52592, P56971, P70174, Q17232, Q28928, Q333S9, Q5E9P3, Q5IS73, Q71SP5, Q7JQF1, Q801M1, Q90WY5, Q98894, Q98895, Q9DDK4, Q9H228, Q9I8K8, Q9N2B0, Q9N2B1, Q9N2B2, Q9PUI7, Q9PUQ8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
S1PR5	“up-regulates activity”	GNAI1	binding
S1PR5	“up-regulates activity”	GNAI3	binding
“sphingosine 1-phosphate(1-)”	“up-regulates activity”	S1PR5	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

71 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

255 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10515025:CAAGG:C	acceptor_gain	1.0000
19:10515028:GG:G	acceptor_gain	1.0000
19:10515029:GC:G	acceptor_loss	1.0000
19:10515030:C:CC	acceptor_gain	1.0000
19:10515030:C:G	acceptor_loss	1.0000
19:10515031:T:C	acceptor_loss	1.0000
19:10517288:C:CA	donor_gain	1.0000
19:10517396:A:AC	donor_gain	1.0000
19:10517397:C:CC	donor_gain	1.0000
19:10515026:AAGG:A	acceptor_gain	0.9900
19:10515027:AGG:A	acceptor_gain	0.9900
19:10515033:T:C	acceptor_gain	0.9900
19:10515033:T:TC	acceptor_gain	0.9900
19:10517397:CT:C	donor_gain	0.9900
19:10517397:CTCTG:C	donor_gain	0.9900
19:10517390:CCACT:C	donor_loss	0.9800
19:10517391:CACTC:C	donor_loss	0.9800
19:10517392:ACTCA:A	donor_loss	0.9800
19:10517393:CT:C	donor_loss	0.9800
19:10517394:TCAC:T	donor_loss	0.9800
19:10517395:CACTC:C	donor_loss	0.9800
19:10517389:TCCAC:T	donor_loss	0.9700
19:10517404:C:CA	donor_gain	0.9600
19:10517289:C:A	donor_gain	0.9500
19:10517396:ACT:A	donor_gain	0.9500
19:10517397:CTC:C	donor_gain	0.9500
19:10517397:CTCT:C	donor_gain	0.9500
19:10517266:T:TA	donor_gain	0.9300
19:10515032:G:C	acceptor_gain	0.8900
19:10515032:G:GC	acceptor_gain	0.8700

AlphaMissense

2465 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10514637:G:C	S125R	0.997
19:10514637:G:T	S125R	0.997
19:10514639:T:G	S125R	0.997
19:10514767:T:A	D82V	0.997
19:10514767:T:C	D82G	0.997
19:10514767:T:G	D82A	0.997
19:10514781:G:C	S77R	0.997
19:10514781:G:T	S77R	0.997
19:10514783:T:G	S77R	0.997
19:10514464:G:A	S183F	0.996
19:10514766:A:C	D82E	0.996
19:10514766:A:T	D82E	0.996
19:10514106:G:C	N302K	0.995
19:10514106:G:T	N302K	0.995
19:10514118:G:C	N298K	0.995
19:10514118:G:T	N298K	0.995
19:10514487:G:C	C175W	0.995
19:10514850:A:C	N54K	0.995
19:10514850:A:T	N54K	0.995
19:10514222:A:G	W264R	0.994
19:10514222:A:T	W264R	0.994
19:10514467:C:T	C182Y	0.994
19:10514756:C:G	G86R	0.994
19:10514232:A:C	F260L	0.993
19:10514232:A:T	F260L	0.993
19:10514234:A:G	F260L	0.993
19:10514464:G:T	S183Y	0.993
19:10514466:G:C	C182W	0.993
19:10514537:A:G	W159R	0.993
19:10514537:A:T	W159R	0.993

dbSNP variants (sampled 300 via entrez): RS1001150558 (19:10513294 C>G,T), RS1001320375 (19:10519115 C>A,T), RS1001535454 (19:10516935 G>A,T), RS1001866094 (19:10518033 C>A), RS1001875917 (19:10518449 C>G), RS1002404707 (19:10518573 T>C), RS1002779900 (19:10518341 C>A), RS1003374193 (19:10517103 G>A), RS1003451624 (19:10515852 C>G,T), RS1003813391 (19:10517344 C>A,G), RS1004043119 (19:10515562 G>A), RS1004104533 (19:10514513 G>A,C,T), RS1004457090 (19:10515680 C>A), RS1004716765 (19:10516484 A>G), RS1005534931 (19:10514864 T>C,G)

Disease associations

OMIM: gene MIM:605146 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010245_13	LDL cholesterol levels	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2274 (SINGLE PROTEIN), CHEMBL2363041 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 19,928 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2336071	SIPONIMOD	4	1,508
CHEMBL314854	FINGOLIMOD	4	16,015
CHEMBL3358920	ETRASIMOD	4	817
CHEMBL3707247	OZANIMOD	4	1,588

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Lysophospholipid (S1P) receptors

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
compound 15 [PMID: 33738061]	Antagonist	10.0	pIC50
AFD(R)	Agonist	9.7	pEC50
fingolimod-phosphate	Agonist	9.22	pIC50
siponimod	Agonist	9.01	pEC50
compound 26 [PMID: 16190743]	Agonist	9.0	pIC50
sphingosine 1-phosphate	Agonist	8.9	pEC50
VPC03090-P	Partial agonist	8.62	pEC50
A-971432	Agonist	8.24	pEC50
RP-101075	Agonist	8.23	pEC50
ASP4058	Agonist	8.12	pEC50
compound 43 [PMID: 26751273]	Agonist	7.78	pEC50
etrasimod	Agonist	7.61	pEC50
VPC44116	Partial agonist	7.5	pEC50
ozanimod	Agonist	7.26	pEC50
GSK2018682	Agonist	7.2	pEC50
ponesimod	Partial agonist	6.85	pIC50
AUY954	Agonist	6.47	pEC50
fingolimod	Agonist	5.68	pIC50

Binding affinities (BindingDB)

96 measured of 144 human assays (144 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)propanoic acid	EC50	0.08 nM
3-(4-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-3-methylphenyl)propanoic acid	EC50	0.08 nM
3-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)butanoic acid	EC50	0.12 nM
(1S,2S)-2-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)cyclopropane-1-carboxylic acid	EC50	0.21 nM
2-methyl-3-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)propanoic acid	EC50	0.3 nM
1-({4-[5-(4-cyclopentylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	0.4 nM
1-[(4-{5-[4-(3,3,3-trifluoropropyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	0.4 nM
3-(5-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-6-methylpyridin-2-yl)propanoic acid	EC50	0.44 nM
(1S,2S)-2-(4-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-3-methylphenyl)cyclopropane-1-carboxylic acid	EC50	0.45 nM
1-[(4-{5-[4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	0.6 nM
1-{[4-(5-{4-[(1R)-3,3-difluorocyclopentyl]phenyl}-1,2,4-oxadiazol-3-yl)phenyl]methyl}azetidine-3-carboxylic acid	IC50	0.8 nM
(1S,2R)-2-(4-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-3-methylphenyl)cyclopropane-1-carboxylic acid	EC50	0.8 nM
1-{[4-(5-{4-[(1S)-3,3-difluorocyclopentyl]phenyl}-1,2,4-oxadiazol-3-yl)phenyl]methyl}azetidine-3-carboxylic acid	IC50	0.9 nM
{[(4Z)-2-amino-3-hydroxyoctadec-4-en-1-yl]oxy}phosphonic acid	KI	1.2 nM
1-(2,6-dichloro-4-pyridinyl)-3-[(3-methyl-4-propan-2-yl-1-prop-2-enylpyrazolo[5,4-b]pyridin-6-yl)amino]urea	IC50	1.2 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-[(4-{5-[4-(2-methylbutan-2-yl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	1.3 nM
1-({4-[5-(4-propylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	1.3 nM
1-({4-[5-(4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	1.4 nM
1-({4-[5-(4-phenylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	1.7 nM
1-[(4-{5-[4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	1.8 nM
[(2S)-2-amino-3-hydroxy-2-[2-(4-octylphenyl)ethyl]propoxy]phosphonic acid	KI	2.1 nM
1-({4-[5-(4-cyclobutylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	2.2 nM
1-({4-[5-(4-butylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	2.9 nM
1-({4-[5-(4-tert-butylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	3.8 nM
1-[(4-{5-[4-(2,2-dimethylpropyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	3.8 nM
1-[2-chloro-6-(ethylamino)-4-pyridinyl]-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(2-hydroxyethyl)amino]urea	IC50	4 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
{2-amino-3-hydroxy-2-[2-(4-octylphenyl)ethyl]propoxy}phosphonic acid	KI	4.1 nM
1-({4-[5-(4-cyclopropylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	4.5 nM
1-(2,6-dichloro-4-pyridinyl)-3-[[3-(3-hydroxypropyl)-1-methyl-7-propan-2-ylpyrazolo[4,5-b]pyridin-5-yl]amino]urea	IC50	5 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-({4-[5-(4-ethoxyphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	5.1 nM
1-(2,6-dichloro-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(2-hydroxyethyl)amino]urea	IC50	7 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-{4-[3-(4-tert-butylphenyl)-1,2,4-oxadiazol-5-yl]benzyl}azetidine-3-carboxylic acid	IC50	8.2 nM
4-[2-[3-fluoro-4-[(2-fluorophenyl)methoxy]phenyl]-6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl]butanoic acid	EC50	10 nM	US-9670220: Fused heterocyclic derivatives as S1P modulators
1-(2-chloro-6-propoxy-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(2-hydroxyethyl)amino]urea	IC50	10 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
2-[[(2,6-dichloro-4-pyridinyl)carbamoylamino]-(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)amino]acetic acid	IC50	11 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-(2,6-dichloro-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)amino]urea	IC50	11 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-(2,6-dichloro-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(3-hydroxypropyl)amino]urea	IC50	19 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-[2-chloro-6-[ethyl(methyl)amino]-4-pyridinyl]-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(2-hydroxyethyl)amino]urea	IC50	19 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-({4-[5-(4-hexylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	29 nM
1-(2-chloro-6-ethoxy-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(2-hydroxyethyl)amino]urea	IC50	29 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
3-[2-[4-[(4-chlorophenyl)methoxy]phenyl]-6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl]-2-methylpropanoic acid	EC50	32 nM	US-9670220: Fused heterocyclic derivatives as S1P modulators
3-[6-[(2-chloro-6-ethylphenyl)methylsulfanyl]-7-fluorospiro[2H-1-benzofuran-3,4’-piperidine]-1’-yl]propanoic acid	EC50	39.8 nM	US-10179791: Spiro-cyclic amine derivatives as S1P modulators
1-(2,6-dichloro-4-pyridinyl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-prop-2-enylamino]urea	IC50	52 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-(2,6-dichloro-4-pyridinyl)-3-(3-methyl-4-propan-2-yl-1-prop-2-enylpyrazolo[5,4-b]pyridin-6-yl)oxyurea	IC50	52 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
1-(4,5-dichlorothiophen-2-yl)-3-[(1,3-dimethyl-4-propan-2-ylpyrazolo[5,4-b]pyridin-6-yl)-(2-hydroxyethyl)amino]urea	IC50	64 nM	US-9663511: Sphingosine 1-phosphate receptor antagonists
3-(7-fluoro-6-octoxyspiro[2H-1-benzofuran-3,4’-piperidine]-1’-yl)propanoic acid	EC50	79.4 nM	US-10179791: Spiro-cyclic amine derivatives as S1P modulators
3-[2-[4-[(2-fluorophenyl)methoxy]phenyl]-6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl]propanoic acid	EC50	100 nM	US-9670220: Fused heterocyclic derivatives as S1P modulators
1-{4-[5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl]benzyl}azetidine-3-carboxylic acid	IC50	100 nM
N-[2-(benzenecarboximidoylamino)-1-(3-chlorophenyl)-2-oxoethyl]-3,5-dichlorobenzamide	IC50	112 nM	US-10323029: Sphinogosine-1-phosphate receptor modulators for treatment of cardiopulmonary disorders
3-[6-[(2-chloro-6-ethylphenyl)methylsulfanyl]spiro[2H-1-benzofuran-3,4’-piperidine]-1’-yl]propanoic acid	EC50	158 nM	US-10179791: Spiro-cyclic amine derivatives as S1P modulators

ChEMBL bioactivities

635 potent at pChembl≥5 of 660 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	EC50	0.03	nM	CHEMBL4787458
10.20	EC50	0.063	nM	CHEMBL4754965
10.00	EC50	0.1	nM	CHEMBL4748198
10.00	EC50	0.1	nM	CHEMBL4798593
9.70	EC50	0.2	nM	CHEMBL225155
9.57	EC50	0.27	nM	CHEMBL4784199
9.52	EC50	0.3	nM	FINGOLIMOD
9.52	EC50	0.3	nM	FTY720-P
9.52	IC50	0.3	nM	CHEMBL381872
9.52	Ki	0.3	nM	CHEMBL4787458
9.48	EC50	0.33	nM	CHEMBL4093489
9.48	EC50	0.33	nM	CHEMBL1091103
9.47	EC50	0.34	nM	FTY720-P
9.44	EC50	0.36	nM	FTY720-P
9.40	IC50	0.4	nM	CHEMBL195014
9.40	EC50	0.4	nM	CHEMBL114606
9.34	EC50	0.46	nM	CHEMBL190006
9.30	IC50	0.5	nM	CHEMBL198976
9.30	IC50	0.5	nM	CHEMBL198415
9.28	EC50	0.53	nM	CHEMBL4458575
9.26	IC50	0.55	nM	CHEMBL225155
9.24	IC50	0.58	nM	CHEMBL184879
9.24	Ki	0.574	nM	CHEMBL4093489
9.22	EC50	0.6	nM	CHEMBL1083828
9.18	EC50	0.66	nM	CHEMBL3102904
9.17	EC50	0.67	nM	CHEMBL114606
9.17	EC50	0.67	nM	FTY720-P
9.15	EC50	0.7	nM	CHEMBL210942
9.14	IC50	0.73	nM	CHEMBL184879
9.11	IC50	0.77	nM	CHEMBL1161691
9.11	IC50	0.77	nM	CHEMBL114606
9.10	IC50	0.8	nM	CHEMBL196534
9.09	EC50	0.81	nM	CHEMBL4747262
9.04	EC50	0.92	nM	CHEMBL4087932
9.04	EC50	0.91	nM	CHEMBL225155
9.02	EC50	0.96	nM	CHEMBL4798181
9.01	EC50	0.98	nM	SIPONIMOD
9.01	EC50	0.98	nM	CHEMBL4095920
9.00	IC50	1	nM	CHEMBL193789
9.00	IC50	1	nM	CHEMBL194419
9.00	IC50	1	nM	CHEMBL3739440
9.00	IC50	1	nM	CHEMBL1973936
9.00	IC50	1	nM	CHEMBL3741092
9.00	IC50	1	nM	CHEMBL1966501
9.00	IC50	1	nM	CHEMBL1990223
8.96	EC50	1.1	nM	CHEMBL4448752
8.96	EC50	1.1	nM	CHEMBL4757160
8.96	IC50	1.1	nM	CHEMBL225155
8.96	IC50	1.1	nM	CHEMBL473269
8.92	IC50	1.2	nM	CHEMBL181597

PubChem BioAssay actives

494 with measured affinity, of 821 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[(4-methyl-2-spiro[4.5]decan-8-yloxynaphthalen-1-yl)methyl]piperidine-4-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	<0.0001	uM
3-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methylamino]cyclobutane-1-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0001	uM
1-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methyl]piperidine-4-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0001	uM
3-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methylamino]propanoic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0001	uM
[(E,2S,3R)-2-amino-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	481653: Displacement of [33P]S1P from human recombinant S1P5 receptor expressed in CHO cells by scintillation counting	ec50	0.0002	uM
Fingolimod	1054252: Agonist activity at S1P5 receptor (unknown origin)	ec50	0.0003	uM
[(2S)-2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	240251: Agonism of human S1P-5 receptor expressed in CHO cells, 90-120 min in pH 7.4 using [35S]GTP-gamma-S as radioligand	ec50	0.0003	uM
1-[[6-[(2-methoxy-4-propylphenyl)methoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid	1477094: Agonist activity at human S1P5 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP accumulation after 30 mins by ELISA	ec50	0.0003	uM
1-[[4-[5-[4-(3,3,3-trifluoropropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0003	uM
[2-amino-3-hydroxy-2-[(2R)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl]propyl] dihydrogen phosphate	473723: Agonist activity at human S1P5 receptor assessed as effect on calcium mobilization by Gq dependent whole cell assay	ec50	0.0003	uM
4-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methylamino]cyclohexane-1-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0003	uM
1-[[4-[5-[4-[(1R)-3,3-difluorocyclopentyl]phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0004	uM
[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	1300070: Agonist activity at human S1P5 receptor by GTPgammaS binding assay	ec50	0.0004	uM
1-[[4-[5-(4-cyclopentylphenyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0005	uM
[(2R)-2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	466806: Agonist activity at human S1P5 receptor expressed in CHO cells assessed as induction of [S35]GTPgammaS binding	ec50	0.0005	uM
1-[[4-[5-[4-[(1S)-3,3-difluorocyclopentyl]phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0005	uM
2-[(3R)-1-[(2S)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidin-3-yl]acetic acid	1626277: Agonist activity at S1P5 receptor (unknown origin) measured after 45 mins by [35S]GTP-gammaS binding assay	ec50	0.0005	uM
2-[5-(4-nonylphenyl)pyrrolidin-2-yl]ethylphosphonic acid	241963: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 5 expressed on CHO cell membranes	ic50	0.0006	uM
1-[[4-[[6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidine-4-carbonyl]amino]-3-methylphenyl]methyl]azetidine-3-carboxylic acid	466264: Agonist activity at S1P5 receptor expressed in CHO cells after 60 mins by [35S]-GTPgammaS binding assay	ec50	0.0006	uM
3-[4-[5-[3-cyano-4-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl]-3-methylphenyl]propanoic acid	268306: Agonist activity at S1P5 receptor expressed in CHO cells measured as S1P-induced [35S]GTP-gamma-S uptake	ec50	0.0007	uM
[(2S)-2-amino-2-[5-[4-octoxy-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]propyl] dihydrogen phosphate	1062162: Agonist activity at human S1P5R expressed in HEK293T cells assessed as [35S]GTPgammaS binding after 30 mins by scintillation counting	ec50	0.0007	uM
[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butoxy]-trihydroxyphosphanium	241963: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 5 expressed on CHO cell membranes	ic50	0.0008	uM
3-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methylamino]cyclopentane-1-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0008	uM
1-[[4-[5-(4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0008	uM
1-[[6-[(2-methoxy-6-propyl-3-pyridinyl)methoxy]-1,5-dimethyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid	1477094: Agonist activity at human S1P5 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP accumulation after 30 mins by ELISA	ec50	0.0009	uM
[(Z)-2-amino-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	1798300: [32P] S1P Binding Assay from Article 10.1016/j.bmc.2004.10.008: “Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate.”	ki	0.0009	uM
1-[[4-[5-(4-butylphenyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	255016: Concentration required for displacement of [33P]-labeled S1P from human sphingosine 1-phosphate receptor 5 expressed in CHO cells	ic50	0.0010	uM
1-[[4-[5-[4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0010	uM
1-[[6-[(2-methoxy-4-propylphenyl)methoxy]-1,5-dimethyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid	1477094: Agonist activity at human S1P5 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP accumulation after 30 mins by ELISA	ec50	0.0010	uM
1-[(4-nonoxyphenyl)methyl]azetidine-3-carboxylic acid	1264656: Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0010	uM
Siponimod	1054245: Agonist activity at human S1P5 receptor expressed in CHO cells by [35S]GTPgammaS binding assay	ec50	0.0010	uM
1-[[4-[(3,4-dichlorophenyl)methoxy]-2-methylphenyl]methyl]azetidine-3-carboxylic acid	1264656: Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0010	uM
1-[[2-methyl-4-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]methyl]azetidine-3-carboxylic acid	1264656: Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0010	uM
1-[[4-[2-[3-(trifluoromethyl)phenyl]ethyl]phenyl]methyl]azetidine-3-carboxylic acid	1264656: Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0010	uM
[(1R,3R)-1-amino-3-(4-octoxyphenyl)cyclopentyl]methyl dihydrogen phosphate	1264656: Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0010	uM
1-[[3-chloro-4-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]methyl]azetidine-3-carboxylic acid	1264656: Displacement of [33P]S1P from S1P5 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0010	uM
1-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methyl]pyrrolidine-3-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0010	uM
[(2R)-2-amino-2-[5-(3-fluoro-4-octoxyphenyl)-1H-imidazol-2-yl]propyl] dihydrogen phosphate	392392: Displacement of [33P]sphingosine-1-phosphate from human S1P5 receptor	ic50	0.0011	uM
(3S)-1-[(2S)-2-hydroxy-2-[4-[5-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]ethyl]piperidine-3-carboxylic acid	1626277: Agonist activity at S1P5 receptor (unknown origin) measured after 45 mins by [35S]GTP-gammaS binding assay	ec50	0.0011	uM
1-[(4-methyl-2-spiro[5.5]undecan-3-yloxynaphthalen-1-yl)methyl]piperidine-4-carboxylic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0011	uM
[(1S,3S)-3-[(4-nonylphenyl)methylamino]cyclohexyl]phosphonic acid	241963: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 5 expressed on CHO cell membranes	ic50	0.0012	uM
[(2R)-2-amino-2-[5-(4-octoxyphenyl)-1H-imidazol-2-yl]propyl] dihydrogen phosphate	392392: Displacement of [33P]sphingosine-1-phosphate from human S1P5 receptor	ic50	0.0014	uM
4-[[2-(4-tert-butylcyclohexyl)oxy-4-methylnaphthalen-1-yl]methylamino]butanoic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0014	uM
3-[(2-hexoxy-4-methylnaphthalen-1-yl)methylamino]propanoic acid	1719721: Antagonist activity at recombinant human S1P5 receptor expressed in Chem-1 cells assessed as EC80 S1P-induced calcium flux measured for 180 secs by FLIPR assay	ec50	0.0014	uM
[(2R)-2-amino-2-[(2S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl]propyl] dihydrogen phosphate	473723: Agonist activity at human S1P5 receptor assessed as effect on calcium mobilization by Gq dependent whole cell assay	ec50	0.0015	uM
1-[[4-[5-(4-propylphenyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0016	uM
1-[[4-[5-[4-(2-methylbutan-2-yl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	1798167: S1P Receptor Binding Assay from Article 10.1021/jm0503244: “Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.”	ic50	0.0018	uM
[(2R)-2-amino-4-(4-heptoxyphenyl)-2-methylbutyl] dihydrogen phosphate	258422: Binding potency at human S1P5 receptor by [35S]GTP-gamma-S binding assay	ec50	0.0020	uM
[(2R)-2-amino-2-methyl-4-[4-[11-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]undecoxy]phenyl]butyl] dihydrogen phosphate	258422: Binding potency at human S1P5 receptor by [35S]GTP-gamma-S binding assay	ec50	0.0020	uM
[(E,2S,3R)-2-amino-3-hydroxypentadec-4-enyl] dihydrogen phosphate	258422: Binding potency at human S1P5 receptor by [35S]GTP-gamma-S binding assay	ec50	0.0020	uM

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
entinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
allyl sulfide	decreases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
sphingosine 1-phosphate	affects binding, decreases reaction, increases activity	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Cannabidiol	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1

ChEMBL screening assays

135 unique, capped per target: 68 functional, 67 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1029038	Binding	Displacement of [33P]sphingosine-1-phosphate from human S1P5 receptor	Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists. — Bioorg Med Chem Lett
CHEMBL1039350	Functional	Agonist activity at human SIP5 receptor by [35S]GTPgammaS binding assay	Pyrazole derived from (+)-3-carene; a novel potent, selective scaffold for sphingosine-1-phosphate (S1P(1)) receptor agonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7ZX	Ubigene A-549 S1PR5 KO	Cancer cell line	Male
CVCL_D9R9	Ubigene HEK293 S1PR5 KO	Transformed cell line	Female
CVCL_RQ10	CHO-K1 (+Gqi5) AequoScreen S1P5	Spontaneously immortalized cell line	Female
CVCL_TJ97	HAP1 S1PR5 (-) 1	Cancer cell line	Male
CVCL_TJ98	HAP1 S1PR5 (-) 2	Cancer cell line	Male
CVCL_ZK33	Tango EDG8-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.