SPHK1

Summary

SPHK1 (sphingosine kinase 1, HGNC:11240) is a protein-coding gene on chromosome 17q25.1, encoding Sphingosine kinase 1 (Q9NYA1). Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions.

The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 8877 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 79 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001142601

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11240
Approved symbol	SPHK1
Name	sphingosine kinase 1
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	SPHK
Ensembl gene	ENSG00000176170
Ensembl biotype	protein_coding
OMIM	603730
Entrez	8877

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 retained_intron

ENST00000323374, ENST00000392496, ENST00000545180, ENST00000587167, ENST00000588682, ENST00000590379, ENST00000590959, ENST00000591651, ENST00000591762, ENST00000592299, ENST00000889756, ENST00000889757, ENST00000889758, ENST00000889759, ENST00000889760, ENST00000889761, ENST00000889762, ENST00000960427, ENST00000960428, ENST00000960429

RefSeq mRNA: 5 — MANE Select: NM_001142601 NM_001142601, NM_001142602, NM_001355139, NM_021972, NM_182965

CCDS: CCDS11744, CCDS45785, CCDS59297

Canonical transcript exons

ENST00000592299 — 6 exons

Exon	Start	End
ENSE00001264903	76385985	76386137
ENSE00002836379	76384609	76384806
ENSE00003469094	76386221	76386315
ENSE00003480633	76386393	76386508
ENSE00003541864	76385451	76385654
ENSE00003900936	76386806	76387855

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3850 / max 308.3490, expressed in 1614 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162832	12.5619	1524
162836	3.5486	810
162831	1.7223	619
162835	1.1568	513
162830	1.1016	471
162838	0.9470	263
162833	0.3375	174
162837	0.2667	148
162829	0.2545	139
162834	0.2265	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.10	gold quality
lower esophagus mucosa	UBERON:0035834	93.09	gold quality
tibial nerve	UBERON:0001323	91.98	gold quality
sural nerve	UBERON:0015488	90.05	gold quality
decidua	UBERON:0002450	88.79	gold quality
esophagus mucosa	UBERON:0002469	86.72	gold quality
minor salivary gland	UBERON:0001830	86.49	gold quality
mucosa of stomach	UBERON:0001199	86.47	gold quality
monocyte	CL:0000576	84.56	gold quality
mouth mucosa	UBERON:0003729	84.37	gold quality
upper lobe of left lung	UBERON:0008952	84.22	gold quality
omental fat pad	UBERON:0010414	84.15	gold quality
peritoneum	UBERON:0002358	84.04	gold quality
mononuclear cell	CL:0000842	84.02	gold quality
left uterine tube	UBERON:0001303	83.94	gold quality
right lung	UBERON:0002167	83.94	gold quality
gall bladder	UBERON:0002110	83.93	gold quality
ascending aorta	UBERON:0001496	83.88	gold quality
skin of leg	UBERON:0001511	83.81	gold quality
thoracic aorta	UBERON:0001515	83.65	gold quality
esophagus	UBERON:0001043	83.63	gold quality
leukocyte	CL:0000738	83.32	gold quality
left coronary artery	UBERON:0001626	82.78	gold quality
skin of abdomen	UBERON:0001416	82.73	gold quality
upper lobe of lung	UBERON:0008948	82.61	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.59	gold quality
descending thoracic aorta	UBERON:0002345	82.56	gold quality
ectocervix	UBERON:0012249	82.04	gold quality
right atrium auricular region	UBERON:0006631	81.95	gold quality
amniotic fluid	UBERON:0000173	81.83	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	39.94
E-MTAB-6701	yes	16.01
E-ANND-3	yes	11.28
E-MTAB-7249	no	46.79
E-MTAB-6678	no	3.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BTG2, EP300, EPAS1, FOS, H4C2, HIF1A, HR, JUN, KLF14, MYB, PAX6, PPARA, SP1, SP6, SPI1, TFAP2A

miRNA regulators (miRDB)

12 targeting SPHK1, 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-5196-5P	100.00	67.98	2761
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6784-3P	98.39	64.88	662

Literature-anchored findings (GeneRIF, showing 40)

• These findings show a role for SphK in the signal transduction by TRAF2 specifically leading to activation of NF-kappa B and antiapoptosis. (PMID:11777919)
• synthesize sphingosine 1-phosphate,a lipid mediator in intracellular signaling system (PMID:11915350)
• results indicate that SPHK1-interacting protein(SKIP) is a novel protein likely to play a regulatory role in the modulation of SPHK1 activity (PMID:12080051)
• activation and translocation to cell membrane dependent on protein kinase C (PMID:12124383)
• characterization of the nucleotide-binding site of human sphingosine kinase 1 through a combination of site-directed mutagenesis and affinity labeling with the ATP analogue, FSBA (PMID:12393916)
• role for sphingosine kinase in the regulation of neutrophil priming (PMID:12444147)
• Resting tone and myogenic responses of isolated hamster resistance arteries increased with forced expression of human Sphk1 in smooth muscle cells (PMID:12847068)
• Activation of this enzyme in mediated by ERK1/2 phoshporylation (PMID:14532121)
• results provide the first evidence of the active nuclear export of SPHK1 and suggest it is mediated by a CRM1-dependent pathway (PMID:14575709)
• Data show that respiratory syncytial virus stimulates sphingosine kinase activity in lung epithelial cells, leading to activation of antiapoptotic sphingosine 1-phosphate and subsequently activation of Akt and extracellular signal-related kinase. (PMID:14742298)
• SK1 is down-regulated by genotoxic stress, and basal SK1 function may be necessary for the maintenance of tumor cell growth (PMID:14988393)
• hereditary neuralgic amyotrophy is not caused by point mutations of sphingosine kinase 1 (PMID:15052627)
• SphK1 mediates TNF-alpha-induced MCP-1 gene expression through a p38 MAPK-dependent pathway and may participate in oscillatory flow-mediated proinflammatory signaling pathway in the vasculature. (PMID:15191888)
• PI3K and ERK/MAPK mediated the activation of sphingosine kinase and would be involved in the HGF-induced migration of endothelial cells. (PMID:15265705)
• SPHK plays an important role in the immune-inflammatory pathologies triggered by anaphylatoxins in human neutrophils (PMID:15302883)
• Comparison of base sequence of SPHK1/Sphk1 in human, mouse, and rat. (PMID:15585953)
• role for SK in the regulation of vascular phenomena that occur under conditions of stress (PMID:15632208)
• SK1 has marked effects on cell function, with plasma membrane-associated SK having a potent inhibitory effect on the G1-S phase transition [SK1] (PMID:15693752)
• SK1 down-regulation by TNF is dependent on the lysosomal pathway of apoptosis and specifically on cathepsin B, which functions as an SK1 protease in cells (PMID:15710602)
• model in which M.tuberc. inhibits both the activation and phagosomal translocation of sphingosine kinase 1 to block the localized Ca2+ transients required for phagosome maturation (PMID:15749892)
• IL-1beta and TNF-alpha induced an early and sustained increase in SPHK activity in INS-1 cells and isolated islets. (PMID:15855330)
• Findings demonstrate a role of SPHK1 activation in proinflammatory signalling and of SPHK1 basal activity in survival of A549 lung carcinoma cells. (PMID:16038795)
• results suggest that SphK1 may be critical for growth, metastasis and chemoresistance of human breast cancers (PMID:16194537)
• the specific plasma membrane localization and activation of SK1 is mediated largely by specific lipid-protein interactions (PMID:16243846)
• For the first time endogenous SK1 is implicated as an important survival enzyme in MCF-7 cells. The biological consequences of knocking down the enzyme are linked to its biochemical role as a regulator of sphingolipid metabolism. (PMID:16507765)
• These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT. (PMID:16516161)
• These findings uncover a new functional role for Sphingosine kinase 1 (SK1), which can control survival/death balance by targeting sphingolipid de novo biosynthesis. (PMID:16529909)
• Data show that protein kinase C-alpha activation in endothelial cells leads to upregulation of sphingosine kinase-1 expression and activity, which is critically involved in the mechanism of endothelial cell migration. (PMID:16571380)
• results suggest that export of Sphk-1a isoform occurs under physiological conditions and may contribute to the establishment of the vascular S1P gradient. (PMID:16623665)
• SK1 is cleaved by cathepsin B in a sequential manner after basic amino acids, and the initial cleavages at the two identified sites, histidine 122 and arginine 199, occur independently of each other. (PMID:17064696)
• SphK-dependent Akt activation plays a significant role in TNF-alpha-induced cyclin D expression and cell proliferation (PMID:17114809)
• IGFBP-3 induces angiogenesis through IGF-I- and SphK1-dependent mechanisms (PMID:17388800)
• the PI3K/AKT/mTOR signaling pathway is involved in regulation of SphK1, with AKT2 playing a key role in PDGF-induced SphK1 expression (PMID:17482291)
• the localization and activity of SK1 are coordinately regulated with actin dynamics during macrophage activation (PMID:17519232)
• BCR/ABL induces SPK1 expression and increases its cellular activity, leading to upregulation of Mcl-1 in CML cells. (PMID:17599053)
• These data suggested that SPHK1 activation by TGF-beta1 leads to Rho-associated myofibroblasts differentiation mediated by transactivated S1P receptors in the lung fibrogenic process. (PMID:17641298)
• the SKase pathway, through the generation of S1P, is critically involved in mediating globular adiponectin-induced endothelial cell activation (PMID:17822721)
• High expression of sphingosine kinase 1 is associated with estrogen receptor negative breast breast cancer. (PMID:18058224)
• These data suggest that differential formation of sphingosine-1-phosphate by SphK1 and SphK2 has distinct and important actions in human mast cells. (PMID:18178871)
• Activation of sphingosine kinase-1 mediates induction of endothelial cell proliferation and angiogenesis by epoxyeicosatrienoic acids. (PMID:18192241)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000100290
mus_musculus	Sphk1	ENSMUSG00000061878
rattus_norvegicus	Sphk1	ENSRNOG00000010626
drosophila_melanogaster	Sk1	FBGN0030300
drosophila_melanogaster	Cerk	FBGN0037315
drosophila_melanogaster	Sk2	FBGN0052484
caenorhabditis_elegans		WBGENE00007918
caenorhabditis_elegans	cerk-1	WBGENE00020398

Paralogs (4): AGK (ENSG00000006530), SPHK2 (ENSG00000063176), CERK (ENSG00000100422), CERKL (ENSG00000188452)

Protein

Protein identifiers

Sphingosine kinase 1 — Q9NYA1 (reviewed: Q9NYA1)

Alternative names: Acetyltransferase SPHK1

All UniProt accessions (4): Q9NYA1, K7EJ32, K7EMA4, Q53ZR5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion. In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway. Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity. In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA. Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.

Subunit / interactions. Interacts with ACY1. Binds to calmodulin. Interacts with SPHKAP. Interacts with CIB1, the interaction occurs in a calcium-dependent manner. Interacts with TRAF2. Interacts with EEF1A1; the interaction enhances SPHK1 kinase activity.

Subcellular location. Cytoplasm. Nucleus. Cell membrane. Endosome membrane. Membrane. Clathrin-coated pit. Synapse.

Tissue specificity. Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Expressed in brain cortex (at protein level).

Activity regulation. Acetyltransferase activity increases in presence of the kinase substrate, sphingosine. In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA. In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NYA1-1	1	yes
Q9NYA1-2	2
Q9NYA1-3	3

RefSeq proteins (5): NP_001136073, NP_001136074, NP_001342068, NP_068807, NP_892010 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR050187	Lipid_Phosphate_FormReg	Family

Pfam: PF00781

Enzyme classification (BRENDA):

• EC 2.7.1.91 — sphingosine kinase (BRENDA: 15 organisms, 102 substrates, 384 inhibitors, 74 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.017–3.8	22
D-ERYTHRO-SPHINGOSINE	0.0025–0.108	12
SPHINGOSINE	0.005–0.108	12
D-(+)-ERYTHRO-SPHINGANINE	0.0034–0.1	4
FTY720	0.018–0.785	4
NITROBENZOXADIAZOLE-LABELED SPHINGOSINE	1–3.6	4
D-ERYTHROSPHINGANINE	0.016	1
DL-ERYTHRO-DIHYDROSPHINGOSINE	0.02	1
L-(-)-THREO-SPHINGANINE	1	1
SPHINGANINE	0.09	1

Catalyzed reactions (Rhea), 5 shown:

• sphinganine + ATP = sphinganine 1-phosphate + ADP + H(+) (RHEA:15465)
• sphing-4-enine + ATP = sphing-4-enine 1-phosphate + ADP + H(+) (RHEA:35847)
• 1-O-hexadecyl-2-amino-sn-glycerol + ATP = 1-O-hexadecyl-2-desoxy-2-amino-sn-glycero-3-phosphate + ADP + H(+) (RHEA:41163)
• a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+) (RHEA:51496)
• L-seryl-[protein] + acetyl-CoA = O-acetyl-L-seryl-[protein] + CoA (RHEA:59392)

UniProt features (65 total): strand 16, helix 15, binding site 9, sequence conflict 8, mutagenesis site 6, modified residue 2, splice variant 2, short sequence motif 2, chain 1, domain 1, turn 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4V24	X-RAY DIFFRACTION	1.8
3VZB	X-RAY DIFFRACTION	2
3VZC	X-RAY DIFFRACTION	2.3
3VZD	X-RAY DIFFRACTION	2.3
4L02	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYA1-F1	91.52	0.84

Functional residue map

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

Catalytic / active sites (1): 81 (proton donor/acceptor)

Ligand- & substrate-binding residues (9): 178; 185; 191; 341–343; 22–24; 54–58; 79–82; 86; 111–113

Post-translational modifications (2): 193, 225

Mutagenesis-validated functional residues (6):

Position	Phenotype
81	loss of enzyme activity.
81	strongly reduced enzyme activity.
82	loss of enzyme activity.
194	loss of binding to negatively charged membranes, diffuse cytosolic distribution.
197–198	abolishes interaction with cib1.
197–198	loss of binding to negatively charged membranes, diffuse cytosolic distribution.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9833482	PKR-mediated signaling
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-390466	Chaperonin-mediated protein folding
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-556833	Metabolism of lipids
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 440 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_REGULATION_OF_VESICLE_FUSION, PID_S1P_S1P1_PATHWAY, BIOCARTA_EDG1_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_VESICLE_ORGANIZATION, GOBP_SPHINGOLIPID_MEDIATED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT

GO Biological Process (48): blood vessel development (GO:0001568), protein acetylation (GO:0006473), sphingosine metabolic process (GO:0006670), inflammatory response (GO:0006954), brain development (GO:0007420), cell population proliferation (GO:0008283), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), calcium-mediated signaling (GO:0019722), regulation of endocytosis (GO:0030100), sphingolipid biosynthetic process (GO:0030148), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), positive regulation of protein ubiquitination (GO:0031398), regulation of interleukin-1 beta production (GO:0032651), positive regulation of interleukin-17 production (GO:0032740), response to tumor necrosis factor (GO:0034612), intracellular signal transduction (GO:0035556), cellular response to vascular endothelial growth factor stimulus (GO:0035924), negative regulation of apoptotic process (GO:0043066), positive regulation of angiogenesis (GO:0045766), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of smooth muscle contraction (GO:0045987), sphingosine biosynthetic process (GO:0046512), sphingoid catabolic process (GO:0046521), positive regulation of fibroblast proliferation (GO:0048146), regulation of phagocytosis (GO:0050764), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), cellular response to hydrogen peroxide (GO:0070301), cellular response to growth factor stimulus (GO:0071363), DNA biosynthetic process (GO:0071897), regulation of neuroinflammatory response (GO:0150077), negative regulation of ceramide biosynthetic process (GO:1900060), positive regulation of p38MAPK cascade (GO:1900745), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), regulation of microglial cell activation (GO:1903978), regulation of endosomal vesicle fusion (GO:1905364), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), lipid metabolic process (GO:0006629), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (15): magnesium ion binding (GO:0000287), lipid kinase activity (GO:0001727), DNA binding (GO:0003677), calmodulin binding (GO:0005516), ATP binding (GO:0005524), lipid binding (GO:0008289), sphingosine kinase activity (GO:0008481), acetyltransferase activity (GO:0016407), sphingosine-1-phosphate receptor activity (GO:0038036), protein phosphatase 2A binding (GO:0051721), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), obsolete D-erythro-sphingosine kinase activity (GO:0017050)

GO Cellular Component (17): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), cilium (GO:0005929), membrane (GO:0016020), endocytic vesicle (GO:0030139), early endosome membrane (GO:0031901), ciliary transition zone (GO:0035869), presynapse (GO:0098793), endosome (GO:0005768), endosome membrane (GO:0010008), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Signal Transduction	2
Sphingolipid metabolism	1
Chaperonin-mediated protein folding	1
VEGFA-VEGFR2 Pathway	1
ESR-mediated signaling	1
Antimicrobial mechanism of IFN-stimulated genes	1
Interferon Signaling	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Protein folding	1
Metabolism of proteins	1
Metabolism of lipids	1
Signaling by VEGF	1
Metabolism	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
intracellular anatomical structure	2
binding	2
cytoplasm	2
membrane	2
endomembrane system	2
cytoplasmic vesicle	2
vasculature development	1
anatomical structure development	1
protein acylation	1
diol metabolic process	1
sphingoid metabolic process	1
defense response	1
central nervous system development	1
animal organ development	1
head development	1
cellular process	1
regulation of cytokine-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
intracellular signaling cassette	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
interleukin-1 beta production	1
regulation of interleukin-1 production	1
positive regulation of cytokine production	1
interleukin-17 production	1
regulation of interleukin-17 production	1

Protein interactions and networks

STRING

2198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPHK1	S1PR3	Q99500	965
SPHK1	S1PR2	O95136	956
SPHK1	TRAF2	Q12933	941
SPHK1	S1PR5	Q9H228	936
SPHK1	S1PR1	P21453	918
SPHK1	SGPL1	O95470	914
SPHK1	SYT1	P21579	880
SPHK1	SPHKAP	Q2M3C7	876
SPHK1	S1PR4	O95977	875
SPHK1	ACY1	Q03154	819
SPHK1	SPTLC1	O15269	810
SPHK1	SPNS2	Q8IVW8	806
SPHK1	SPTLC2	O15270	768
SPHK1	SPTLC3	Q9NUV7	768
SPHK1	ASAH1	Q13510	766

IntAct

25 interactions, top by confidence:

A	B	Type	Score
KLHL5	CUL3	psi-mi:“MI:0914”(association)	0.800
SPHK1	SPHKAP	psi-mi:“MI:0915”(physical association)	0.600
SPHKAP	SPHK1	psi-mi:“MI:0403”(colocalization)	0.600
FHL2	SPHK1	psi-mi:“MI:0915”(physical association)	0.540
SPHK1	FHL2	psi-mi:“MI:0403”(colocalization)	0.540
SPHK1	EEF1A1	psi-mi:“MI:0407”(direct interaction)	0.540
EEF1A1	SPHK1	psi-mi:“MI:0915”(physical association)	0.540
SPHK1	KLHL5	psi-mi:“MI:0915”(physical association)	0.480
SPHK1	CTSB	psi-mi:“MI:0194”(cleavage reaction)	0.440
CTSB	SPHK1	psi-mi:“MI:0194”(cleavage reaction)	0.440
FYN	SPHK1	psi-mi:“MI:0407”(direct interaction)	0.440
TRAF6	SPHK1	psi-mi:“MI:0915”(physical association)	0.400
RARG	SPHK1	psi-mi:“MI:0915”(physical association)	0.370
SPHK1	ALDH3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): DCXR (Affinity Capture-MS), PPM1G (Affinity Capture-MS), DHPS (Affinity Capture-MS), CYLD (Affinity Capture-MS), SPHK1 (Affinity Capture-Western), CYLD (Affinity Capture-MS), DCXR (Affinity Capture-MS), DHPS (Affinity Capture-MS), SPHK1 (Affinity Capture-Western), BECN1 (Affinity Capture-Western), TRAF2 (Affinity Capture-Western), SPHK1 (Affinity Capture-Western), SPHK1 (Negative Genetic), SPHK1 (Negative Genetic), SPHK1 (Negative Genetic)

ESM2 similar proteins: A0A0U1RPR8, A0JNU3, A6H603, A6QQ74, F1MH07, O43542, O77667, O88202, P0C869, P0DPE1, P10937, P51839, P51840, P52785, P52824, Q2V057, Q3UQ84, Q4KM32, Q5RCH4, Q643R3, Q68DD2, Q68FW7, Q6NVG1, Q6P5E8, Q6QHF9, Q7ZW00, Q7ZYJ3, Q865R1, Q86U10, Q8C0L6, Q8CI15, Q8K4F6, Q8NFF5, Q8R123, Q8TDZ2, Q8VCZ9, Q8VDP3, Q91V26, Q91ZJ0, Q95LP4

Diamond homologs: C0LT23, O14159, O31502, Q18425, Q6B516, Q6USK2, Q8CI15, Q8TCT0, Q91V26, Q9JIA7, Q9LRB0, Q9NRA0, Q9NYA1, F2Y4A3, Q06147, Q10123, Q7ZW00, Q7ZYJ3, Q8K4Q7, Q8L7L1, O34799, A5IU64, A6QIC6, A6U302, A7X424, A8Z2R1, B9DMT6, Q2FFJ7, Q2FWZ2, Q2YU29, Q49VS2, Q49YU2, Q4L7L1, Q53H12, Q5HEM4, Q5HN36, Q5RED7, Q6G835, Q6GFF9, Q7A0H3

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
ERK1/2	up-regulates	SPHK1	phosphorylation
MAPK1	up-regulates	SPHK1	phosphorylation
MAPK3	up-regulates	SPHK1	phosphorylation
KLF14	“up-regulates quantity by expression”	SPHK1	“transcriptional regulation”
Gbeta	up-regulates	SPHK1	phosphorylation
EIF2AK2	“up-regulates activity”	SPHK1	phosphorylation
hsa-miR-101-5p	“down-regulates quantity by repression”	SPHK1	“post transcriptional regulation”
hsa-miR-506-5p	“down-regulates quantity by repression”	SPHK1	“post transcriptional regulation”
hsa-miR-125b-5p	“down-regulates quantity by repression”	SPHK1	“post transcriptional regulation”
hsa-miR-124-5p	“down-regulates quantity by repression”	SPHK1	“post transcriptional regulation”
FHL2	“down-regulates activity”	SPHK1	binding
RPS6KC1	“up-regulates activity”	SPHK1	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

586 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76385637:TCG:T	donor_gain	1.0000
17:76385650:TCCAG:T	donor_loss	1.0000
17:76385651:CCAGG:C	donor_loss	1.0000
17:76385653:AGGTT:A	donor_loss	1.0000
17:76385654:GG:G	donor_loss	1.0000
17:76385655:G:T	donor_loss	1.0000
17:76385805:G:GT	donor_gain	1.0000
17:76385983:A:AG	acceptor_gain	1.0000
17:76385983:AGC:A	acceptor_gain	1.0000
17:76385983:AGCG:A	acceptor_gain	1.0000
17:76385984:G:GA	acceptor_gain	1.0000
17:76385984:GC:G	acceptor_gain	1.0000
17:76385984:GCG:G	acceptor_gain	1.0000
17:76385984:GCGG:G	acceptor_gain	1.0000
17:76386133:CACTG:C	donor_gain	1.0000
17:76386134:ACTG:A	donor_gain	1.0000
17:76386135:CTG:C	donor_gain	1.0000
17:76386136:TG:T	donor_gain	1.0000
17:76386137:GG:G	donor_gain	1.0000
17:76386138:G:GG	donor_gain	1.0000
17:76386138:GT:G	donor_loss	1.0000
17:76386215:CTGCA:C	acceptor_loss	1.0000
17:76386216:TGCA:T	acceptor_loss	1.0000
17:76386217:GCAG:G	acceptor_loss	1.0000
17:76386218:CA:C	acceptor_loss	1.0000
17:76386218:CAG:C	acceptor_gain	1.0000
17:76386219:A:AG	acceptor_gain	1.0000
17:76386219:AGA:A	acceptor_gain	1.0000
17:76386219:AGAGC:A	acceptor_gain	1.0000
17:76386220:G:A	acceptor_loss	1.0000

AlphaMissense

2455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:76387414:G:C	R328P	0.991
17:76386972:A:C	S181R	0.986
17:76386974:T:A	S181R	0.986
17:76386974:T:G	S181R	0.986
17:76386945:G:C	G172R	0.985
17:76386942:T:A	W171R	0.984
17:76386942:T:C	W171R	0.984
17:76387176:T:A	W249R	0.983
17:76387176:T:C	W249R	0.983
17:76387005:T:C	F192L	0.982
17:76387007:C:A	F192L	0.982
17:76387007:C:G	F192L	0.982
17:76386933:A:C	S168R	0.981
17:76386935:C:A	S168R	0.981
17:76386935:C:G	S168R	0.981
17:76386946:G:A	G172D	0.981
17:76387291:T:C	L287P	0.980
17:76387411:T:C	F327S	0.980
17:76387065:T:G	Y212D	0.978
17:76386299:A:T	D81V	0.977
17:76387417:T:C	L329S	0.977
17:76386457:T:A	L108H	0.975
17:76386406:T:C	L91P	0.974
17:76386955:C:A	A175D	0.974
17:76387407:G:C	A326P	0.974
17:76386489:T:C	S119P	0.973
17:76387054:G:A	G208D	0.972
17:76387210:T:A	V260D	0.972
17:76387486:G:A	G352D	0.972
17:76386298:G:C	D81H	0.971

dbSNP variants (sampled 300 via entrez): RS1000206555 (17:76385809 G>A,C,T), RS1001069439 (17:76382497 G>C), RS1001163754 (17:76385028 C>T), RS1001490365 (17:76382021 C>G), RS1001502457 (17:76382363 G>T), RS1002032342 (17:76386639 C>T), RS1002636858 (17:76387755 C>G,T), RS1002834167 (17:76383627 A>C), RS1003116732 (17:76383503 T>C), RS1003167407 (17:76382597 G>A,C), RS1003394311 (17:76388086 C>T), RS1003491819 (17:76384142 A>G), RS1003773815 (17:76387864 G>A), RS1004456868 (17:76383444 G>A), RS1004798342 (17:76387376 A>G,T)

Disease associations

OMIM: gene MIM:603730 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST004611_129	High light scatter reticulocyte count	2.000000e-29
GCST004612_77	High light scatter reticulocyte percentage of red cells	9.000000e-29
GCST004619_132	Reticulocyte fraction of red cells	2.000000e-27
GCST004619_61	Reticulocyte fraction of red cells	3.000000e-22
GCST004622_57	Reticulocyte count	5.000000e-26
GCST004622_58	Reticulocyte count	1.000000e-22
GCST004627_177	Lymphocyte count	5.000000e-14
GCST004628_22	Immature fraction of reticulocytes	7.000000e-22
GCST90002385_320	High light scatter reticulocyte count	2.000000e-14
GCST90002385_321	High light scatter reticulocyte count	3.000000e-40
GCST90002386_194	High light scatter reticulocyte percentage of red cells	6.000000e-12
GCST90002386_195	High light scatter reticulocyte percentage of red cells	3.000000e-42
GCST90002387_199	Immature fraction of reticulocytes	4.000000e-32
GCST90002388_508	Lymphocyte count	6.000000e-26
GCST90002388_509	Lymphocyte count	2.000000e-30
GCST90002394_414	Monocyte percentage of white cells	3.000000e-13
GCST90002396_672	Mean reticulocyte volume	1.000000e-16
GCST90002398_312	Neutrophil count	5.000000e-09
GCST90002404_178	Red cell distribution width	3.000000e-12
GCST90002405_390	Reticulocyte count	8.000000e-45
GCST90002405_391	Reticulocyte count	1.000000e-34
GCST90002406_470	Reticulocyte fraction of red cells	4.000000e-52
GCST90002406_471	Reticulocyte fraction of red cells	1.000000e-35
GCST90002407_152	White blood cell count	5.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4394 (SINGLE PROTEIN), CHEMBL4680050 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 109,907 (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
CHEMBL50	QUERCETIN	3	74,559
CHEMBL1442934	SAFINGOL	2	12,200
CHEMBL6246	ELLAGIC ACID	2	23,148

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Sphingosine kinase

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
PF-543	Inhibition	8.44	pKi
compound 49 [PMID: 30889352]	Inhibition	7.85	pIC50
compound 28 [PMID: 35439002]	Inhibition	7.72	pIC50
SKI II	Inhibition	6.3	pIC50
compound 59 [PMID: 30889352]	Inhibition	6.12	pIC50
compound 60 [PMID: 30889352]	Inhibition	5.63	pIC50
compound 55 [PMID: 30889352]	Inhibition	5.38	pIC50
SLM6071469	Inhibition	5.19	pKi
SLC4101431	Inhibition	5.05	pKi
compound 27d [PMID: 28231433]	Inhibition	5.01	pIC50
MP-A08	Inhibition	4.57	pIC50

Binding affinities (BindingDB)

52 measured of 112 human assays (112 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-1-[4-[7-(cyclohexylmethoxy)heptyl]benzoyl]-N’-hydroxypyrrolidine-2-carboximidamide	KI	75 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-(4-dodecylbenzoyl)pyrrolidine-2-carboximidamide	KI	100 nM	US-9688668: Long chain base sphingosine kinase inhibitors
(2S)-1-(4-dodecylbenzoyl)-N’-hydroxypyrrolidine-2-carboximidamide	KI	100 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[10-(cyclohexylmethoxy)decyl]-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	110 nM	US-9421177: Imidamide sphingosine kinase inhibitors
4-[7-(cyclohexylmethoxy)heptyl]-N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]benzamide	KI	130 nM	US-9421177: Imidamide sphingosine kinase inhibitors
4-[7-(cyclopentylmethoxy)heptyl]-N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]benzamide	KI	170 nM	US-9421177: Imidamide sphingosine kinase inhibitors
4-dodecyl-N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]benzamide	KI	200 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[4-[7-(cyclohexylmethoxy)heptyl]phenyl]-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	240 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-(4-dodecylphenyl)-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	300 nM	US-9421177: Imidamide sphingosine kinase inhibitors
(2S)-N’-hydroxy-1-(4-undecylbenzoyl)pyrrolidine-2-carboximidamide	KI	300 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[4-[6-(cyclohexylmethoxy)hexyl]phenyl]-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	390 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-(4-undecylphenyl)cyclopropane-1-carboxamide	KI	400 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[10-(cyclopentylmethoxy)decyl]-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	450 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-[4-(9-phenylnonyl)phenyl]cyclopropane-1-carboxamide	KI	500 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]hexadecanamide	KI	750 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[4-[8-(cyclohexylmethoxy)octyl]phenyl]-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	800 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-[4-(8-phenyloctyl)phenyl]cyclopropane-1-carboxamide	KI	1300 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[4-[7-(1-adamantylmethoxy)heptyl]phenyl]-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	1500 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-(4-(7-((Adamantan-1-ylmethoxy)heptyl)phenyl)-1-carbamimidoylcyclopropanecarboxamide Hydrochloride	KI	1500 nM
CHEMBL2407197	EC50	1900 nM
N-(4-decylphenyl)-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	3000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
CHEMBL3287037	KI	3100 nM
CHEMBL3814457	KI	3200 nM
N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]-4-undecoxybenzamide	KI	4000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
4-decyl-N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]benzamide	KI	5000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-[4-(7-phenylmethoxyheptyl)phenyl]cyclopropane-1-carboxamide	KI	5000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
(2S)-1-(4-decylbenzoyl)-N’-hydroxypyrrolidine-2-carboximidamide	KI	5000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-hexadecyl-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	5400 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-tetradecylcyclopropane-1-carboxamide	KI	6000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
(Z)-N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]octadec-9-enamide	KI	8000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-(4-tetradecylphenyl)cyclopropane-1-carboxamide	KI	8400 nM	US-9421177: Imidamide sphingosine kinase inhibitors
1-[(Z)-N’-hydroxycarbamimidoyl]-N-octadecylcyclopropane-1-carboxamide	KI	9000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]-4-tetradecylbenzamide	KI	10000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
(2S)-2-[3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide	KI	12000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
(2R)-1-(4-dodecylbenzoyl)-N’-hydroxypyrrolidine-2-carboximidamide	KI	16000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]-4-octylbenzamide	KI	25000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-(4-hexadecylphenyl)-1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropane-1-carboxamide	KI	30000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
4-hexadecyl-N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]benzamide	KI	36000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
N-[1-[(Z)-N’-hydroxycarbamimidoyl]cyclopropyl]-4-tridecoxybenzamide	KI	40000 nM	US-9421177: Imidamide sphingosine kinase inhibitors
heptadecanimidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
1-[3-(4-decylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropane-1-carboximidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
1-[3-(4-undecylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropane-1-carboximidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
1-[3-(4-dodecylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropane-1-carboximidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
2-[4-(4-octylphenyl)cyclohexyl]guanidine	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
2-[[3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl]methyl]guanidine	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
2-[(1S)-1-[3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl]ethyl]guanidine	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
2-[(1S)-2-methyl-1-[3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl]propyl]guanidine	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
(2S,3S)-3-hydroxy-2-[3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
(S)-2-(3-(4-decylphenyl)-1,2,4-oxadiazol- 5-yl)pyrrolidine-1-carboximidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors
(2S)-2-[3-(4-decylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboximidamide	KI	55000 nM	US-9688668: Long chain base sphingosine kinase inhibitors

ChEMBL bioactivities

427 potent at pChembl≥5 of 545 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	IC50	0.03	nM	CHEMBL4077280
10.52	IC50	0.03	nM	CHEMBL4066270
9.77	IC50	0.17	nM	CHEMBL4061789
9.52	IC50	0.3	nM	CHEMBL4090361
9.22	IC50	0.6	nM	CHEMBL4086094
9.15	IC50	0.7	nM	CHEMBL4066270
9.10	IC50	0.8	nM	CHEMBL4086094
9.10	IC50	0.8	nM	CHEMBL3134157
9.00	IC50	1	nM	CHEMBL4063424
8.82	IC50	1.5	nM	CHEMBL4066270
8.77	IC50	1.7	nM	CHEMBL4069327
8.77	IC50	1.7	nM	CHEMBL4104017
8.70	IC50	2	nM	CHEMBL4061789
8.70	IC50	2	nM	CHEMBL3134157
8.70	IC50	2	nM	CHEMBL4090361
8.62	IC50	2.4	nM	CHEMBL4090361
8.59	IC50	2.6	nM	CHEMBL4077280
8.59	IC50	2.6	nM	CHEMBL3134157
8.57	IC50	2.7	nM	CHEMBL3134157
8.52	IC50	3	nM	CHEMBL2409850
8.52	IC50	3	nM	CHEMBL2409847
8.52	IC50	3	nM	CHEMBL3134157
8.52	IC50	3	nM	CHEMBL4077280
8.46	IC50	3.5	nM	CHEMBL4103414
8.44	Ki	3.6	nM	CHEMBL3134157
8.44	IC50	3.6	nM	CHEMBL3134157
8.41	IC50	3.9	nM	CHEMBL4063424
8.40	IC50	4	nM	CHEMBL2409849
8.40	Ki	4	nM	CHEMBL3134157
8.40	IC50	4	nM	CHEMBL4091588
8.40	IC50	4	nM	CHEMBL4086161
8.37	Ki	4.3	nM	CHEMBL3348835
8.37	Ki	4.3	nM	CHEMBL3134157
8.35	IC50	4.5	nM	CHEMBL4104017
8.32	IC50	4.8	nM	CHEMBL4086094
8.30	IC50	5	nM	CHEMBL2409848
8.30	IC50	5	nM	CHEMBL2407197
8.30	IC50	5	nM	CHEMBL2409886
8.30	Kd	5	nM	CHEMBL3134157
8.28	IC50	5.3	nM	CHEMBL4103414
8.28	IC50	5.2	nM	CHEMBL4077280
8.19	IC50	6.4	nM	CHEMBL4061789
8.15	IC50	7	nM	CHEMBL2409889
8.15	IC50	7	nM	CHEMBL4086161
8.14	Ki	7.2	nM	CHEMBL3814580
8.10	IC50	8	nM	CHEMBL2409888
8.10	IC50	8	nM	CHEMBL4091588
8.10	Ki	8	nM	CHEMBL4783605
8.05	IC50	9	nM	CHEMBL4474024
8.00	IC50	10	nM	CHEMBL2407198

PubChem BioAssay actives

394 with measured affinity, of 1264 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
[(2R)-1-[[4-[(3-cyclohexylphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	<0.0001	uM
(3S)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-3-ol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	<0.0001	uM
(3R,4R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidine-3,4-diol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0002	uM
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0003	uM
[(2R)-1-[[4-[(3-propan-2-ylphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0006	uM
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0008	uM
(3R,4S)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidine-3,4-diol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0010	uM
[(2R)-1-[[4-[[3-(cyclopropylsulfonylmethyl)phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0017	uM
[(2R)-1-[[4-[[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0017	uM
(2R,4S)-1-[2-[4-[[4-(2,4-dichlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0030	uM
(2R,4S)-1-[2-[4-[[4-[2-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0030	uM
2-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methylamino]ethanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0035	uM
[(2R)-1-[[4-[2-methyl-3-(3-methylbutyl)benzimidazol-5-yl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0040	uM
[(2R)-1-[[4-[3-(2-cyclobutylethyl)-2-methylbenzimidazol-5-yl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0040	uM
(2R,4S)-1-[2-[4-[[4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0040	uM
[(2S)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1151452: Competitive inhibition of C-terminal His6-tagged human recombinant SphK1 expressed in baculovirus-infected Sf9 cells using sphingosine as substrate	ki	0.0043	uM
(2R,4S)-1-[2-[4-[[4-[2-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0050	uM
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[[4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]ethyl]piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0050	uM
(2R,4S)-1-[2-[4-[[4-(1-adamantyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0050	uM
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[[4-(4-methylphenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0070	uM
(2S)-2-[3-(6-butoxynaphthalen-2-yl)-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide;hydrochloride	1730246: Inhibition of recombinant human Sphk1 expressed in baculovirus infected Sf9 insect cells using d-erythro-sphingosine as substrate measured after 20 mins in presence of [gamma-32P]ATP by liquid scintillation counting analysis	ki	0.0072	uM
(2S)-2-[3-(1-dodecylindol-3-yl)-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide;hydrochloride	1730246: Inhibition of recombinant human Sphk1 expressed in baculovirus infected Sf9 insect cells using d-erythro-sphingosine as substrate measured after 20 mins in presence of [gamma-32P]ATP by liquid scintillation counting analysis	ki	0.0080	uM
(2R,4S)-1-[2-[4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0080	uM
[(2R)-1-[[4-[[3-[(3-fluorophenyl)methoxy]phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1593533: Inhibition of GFP-tagged SK1 (unknown origin) expressed in HEK293 cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis	ic50	0.0090	uM
[(2R)-1-[[4-[3-(cyclopentylmethyl)-2-methylbenzimidazol-5-yl]phenyl]methyl]pyrrolidin-2-yl]methanol	1442127: Inhibition of SPHK1 in human MDA1483 cells using C17-sphingosine as substrate assessed as reduction in C17-S1P formation preincubated for 30 mins with substrate measured after 15 mins by LC-MS analysis	ic50	0.0100	uM
(2S,3S)-N-[(1S)-1-[4-[5-(2-cyclohexylethyl)-1,2,4-oxadiazol-3-yl]phenyl]propyl]-3-hydroxypyrrolidine-2-carboxamide	493821: Inhibition of sphingosine kinase 1	ic50	0.0100	uM
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]ethyl]piperidin-4-ol	1304651: Inhibition of human SphK1 using sphingosine as substrate incubated for 50 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ic50	0.0100	uM
(2R,4S)-1-[2-[4-[[4-(2-chlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0100	uM
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[[4-(3-methylphenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0100	uM
(2R,4S)-1-[2-[4-[(4-cyclohexyl-1,3-thiazol-2-yl)amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0100	uM
[3-[[4-[[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]phenyl]methoxy]phenyl] benzenesulfonate	1593533: Inhibition of GFP-tagged SK1 (unknown origin) expressed in HEK293 cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis	ic50	0.0110	uM
[(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1593533: Inhibition of GFP-tagged SK1 (unknown origin) expressed in HEK293 cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis	ic50	0.0140	uM
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-4-bromo-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1908691: Inhibition of SPHK1 (unknown origin) using sphingosine-fluorescein as substrate incubated for 1 hr in presence of ATP by mobility shift assay	ic50	0.0198	uM
(3S,5R)-5-(hydroxymethyl)-1-[3-[4-[[4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino]phenyl]propyl]pyrrolidin-3-ol	1277461: Inhibition of SK1 (unknown origin)	ic50	0.0200	uM
(2S,3S)-N-[(1S)-1-[4-[5-(2-cyclohexylethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]-3-hydroxypyrrolidine-2-carboxamide	493821: Inhibition of sphingosine kinase 1	ic50	0.0200	uM
(2R,4S)-1-[2-[4-[[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	1908780: Inhibition of human SPHK1 by biochemical assay	ic50	0.0200	uM
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[(4-naphthalen-2-yl-1,3-thiazol-2-yl)amino]phenyl]ethyl]piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0200	uM
(2R,4S)-1-[2-[4-[[4-(2-fluorophenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0200	uM
(2R,4S)-1-[2-[4-[[4-(3-chlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]-2-(hydroxymethyl)piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0200	uM
(2S,3S)-N-[[4-[5-(2-cyclohexylethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-3-hydroxypyrrolidine-2-carboxamide	493821: Inhibition of sphingosine kinase 1	ic50	0.0250	uM
[(2R)-1-[[4-[[3-(2-phenylethyl)phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1593533: Inhibition of GFP-tagged SK1 (unknown origin) expressed in HEK293 cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis	ic50	0.0260	uM
(3R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-3-ol	1442125: Inhibition of human C-terminal His6-tagged SPHK1 expressed in fall armyworm sf9 cells assessed as reduction in ADP formation using sphingosine as substrate preincubated for 15 mins followed by substrate addition after 1 hr by transcreener-based fluorescence polarization assay	ic50	0.0280	uM
(2S,3S)-N-[(1S)-1-[4-(5-heptyl-1,2,4-oxadiazol-3-yl)phenyl]propyl]-3-hydroxypyrrolidine-2-carboxamide	493821: Inhibition of sphingosine kinase 1	ic50	0.0300	uM
(3R,5R)-1-[3-[4-[[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]propyl]-5-(hydroxymethyl)pyrrolidin-3-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0300	uM
(3S,5R)-1-[3-[4-[[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]amino]phenyl]propyl]-5-(hydroxymethyl)pyrrolidin-3-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0300	uM
(2R,4S)-2-(hydroxymethyl)-1-[2-[4-[[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino]phenyl]ethyl]piperidin-4-ol	762559: Inhibition of purified human SphK1 assessed as inhibition of formation of [33P]-S1P after 50 mins by scintillation counting	ic50	0.0300	uM
[(2R)-1-[[4-[[3-[(2-chlorophenyl)methoxy]phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1593533: Inhibition of GFP-tagged SK1 (unknown origin) expressed in HEK293 cells using Sph as substrate measured after 30 mins in presence of [gamma32P]ATP by Cerenkov counting analysis	ic50	0.0390	uM
[(2R)-1-[[4-[[3-[(4-fluorophenyl)sulfonylmethyl]-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol	1908691: Inhibition of SPHK1 (unknown origin) using sphingosine-fluorescein as substrate incubated for 1 hr in presence of ATP by mobility shift assay	ic50	0.0395	uM
2-[(E)-1,3-dihydroxyoctadec-4-en-2-yl]guanidine;hydrochloride	1923906: Inhibition of SphK1 (unknown origin) assessed as inhibition constant	ki	0.0400	uM
2-[(E,2R,3S)-1,3-dihydroxyoctadec-4-en-2-yl]guanidine;hydrochloride	1151445: Inhibition of SphK1 (unknown origin)	ic50	0.0400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects localization, decreases activity, decreases abundance, increases abundance, decreases reaction (+4 more)	7
Valproic Acid	affects cotreatment, increases expression, increases methylation	5
sodium arsenite	increases abundance, increases expression	4
Estradiol	affects expression, affects cotreatment, increases expression	4
Particulate Matter	increases reaction, decreases expression, increases abundance, increases expression, affects cotreatment (+1 more)	4
trichostatin A	affects cotreatment, increases expression	3
sphingosine 1-phosphate	affects localization, decreases abundance, decreases activity, decreases expression, decreases reaction (+1 more)	3
N,N-dimethylsphingosine	decreases activity, decreases expression	3
Arsenic	affects methylation, increases abundance, increases expression	3
Benzo(a)pyrene	increases expression	3
Tobacco Smoke Pollution	increases expression	3
kaempferol	decreases expression, decreases reaction	2
cobaltous chloride	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cadmium	increases expression	2
Calcium	decreases reaction, increases abundance, increases activity, increases localization	2
Ceramides	decreases activity, affects localization, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
1-Methyl-4-phenylpyridinium	decreases reaction, decreases activity, decreases expression, increases reaction	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression	2
Asbestos, Crocidolite	increases expression, affects expression	2
1-Butanol	affects cotreatment, increases abundance, increases expression, decreases reaction, increases activity	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1

ChEMBL screening assays

232 unique, capped per target: 228 binding, 3 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032133	Binding	Inhibition of SphK1	Iodophenyl tagged sphingosine derivatives: synthesis and preliminary biological evaluation. — Bioorg Med Chem Lett
CHEMBL807606	Functional	Rate of phosphorylation of labeled sphingosine derivative by human SPHK-1 expressed in HEK293 cells relative to rate of D-sphingosine	Fluorescence-labeled sphingosines as substrates of sphingosine kinases 1 and 2. — Bioorg Med Chem Lett
CHEMBL4672286	ADMET	Prodrug conversion in human blood assessed as SPHK1/SPHK2-mediated compound phosphorylation by measuring intrinsic clearance by LC-MS/MS analysis	Design and synthesis of analogues of the sphingosine-1-phosphate receptor 1 agonist IMMH001 with improved phosphorylation rate in human blood. — Bioorg Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Z5	Abcam A-549 SPHK1 KO	Cancer cell line	Male
CVCL_D2D7	Abcam HCT 116 SPHK1 KO	Cancer cell line	Male
CVCL_D2P8	Abcam THP-1 SPHK1 KO	Cancer cell line	Male
CVCL_D8BC	Ubigene A-549 SPHK1 KO	Cancer cell line	Male
CVCL_D8W3	Ubigene HCT 116 SPHK1 KO	Cancer cell line	Male
CVCL_D9SV	Ubigene HEK293 SPHK1 KO	Transformed cell line	Female
CVCL_E0PT	Ubigene HeLa SPHK1 KO	Cancer cell line	Female
CVCL_E2KQ	HAP1 SPHK1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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