Top ▲

sphingosine kinase 1

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2204

Nomenclature: sphingosine kinase 1

Abbreviated Name: SPHK1

Family: Sphingosine kinase

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 384 17q25.2 SPHK1 sphingosine kinase 1
Mouse - 382 11 E2 Sphk1 sphingosine kinase 1
Rat - 383 10 q32.3 Sphk1 sphingosine kinase 1
Previous and Unofficial Names Click here for help
SK1 | SPHK
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.7.1.91 Sphingosine + ATP = sphingosine 1-phosphate + ADP
dihydrosphingosine + ATP = sphingosine 1-phosphate + ADP
Cofactors Click here for help
Cofactor Species Comments Reference
Mg2+ None

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF-543 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pKi 8
pKi 8.4 (Ki 3.6x10-9 M) [8]
SLM6071469 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.2 pKi 9
pKi 5.2 (Ki 6.5x10-6 M) [9]
SLC4101431 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.1 pKi 2
pKi 5.1 (Ki 9x10-6 M) [2]
SKI II Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.8 pKi 4
pKi 4.8 (Ki 1.6x10-5 M) [4]
PF-543 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 – 8.7 pIC50 7-8
pIC50 8.7 (IC50 2x10-9 M) [8]
pIC50 8.6 (IC50 2.7x10-9 M) [7]
compound 49 [PMID: 30889352] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 1
pIC50 7.8 (IC50 1.4x10-8 M) [1]
SKI II Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 3
pIC50 6.3 (IC50 5x10-7 M) [3]
Description: Measured using a GST-hSPHK1 fusion protein
compound 59 [PMID: 30889352] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 1
pIC50 6.1 (IC50 7.65x10-7 M) [1]
compound 60 [PMID: 30889352] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.6 pIC50 1
pIC50 5.6 (IC50 2.36x10-6 M) [1]
compound 55 [PMID: 30889352] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.4 pIC50 1
pIC50 5.4 (IC50 4.13x10-6 M) [1]
compound 27d [PMID: 28231433] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.0 pIC50 7
pIC50 5.0 (IC50 9.82x10-6 M) [7]
MP-A08 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.6 pIC50 6
pIC50 4.6 (IC50 2.7x10-5 M) [6]
Description: In vitro inhibition of substrate phosphorylation.
SK1-I Small molecule or natural product Hs Inhibition - - 5
[5]
Immunopharmacology Comments
The sphingosine kinases (SPHK1 and SPHK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation.
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0030100 regulation of endocytosis IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0150077 regulation of neuroinflammatory response ISS
GO:1903978 regulation of microglial cell activation ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway IDA
GO:0032740 positive regulation of interleukin-17 production ISS
GO:0034612 response to tumor necrosis factor IDA
GO:0070555 response to interleukin-1 IEP
click arrow to show/hide IEA associations
GO:0032651 regulation of interleukin-1 beta production IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0031398 positive regulation of protein ubiquitination IDA
GO:1903978 regulation of microglial cell activation ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes, IEA only
GO:0050764 regulation of phagocytosis ISS
GO:0150077 regulation of neuroinflammatory response ISS
GO:1903978 regulation of microglial cell activation ISS
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA

References

Show »

1. Adams DR, Tawati S, Berretta G, Rivas PL, Baiget J, Jiang Z, Alsfouk A, Mackay SP, Pyne NJ, Pyne S. (2019) Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2. J. Med. Chem., 62 (7): 3658-3676. [PMID:30889352]

2. Childress ES, Kharel Y, Brown AM, Bevan DR, Lynch KR, Santos WL. (2017) Transforming Sphingosine Kinase 1 Inhibitors into Dual and Sphingosine Kinase 2 Selective Inhibitors: Design, Synthesis, and in Vivo Activity. J. Med. Chem., 60 (9): 3933-3957. [PMID:28406646]

3. French KJ, Schrecengost RS, Lee BD, Zhuang Y, Smith SN, Eberly JL, Yun JK, Smith CD. (2003) Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res., 63 (18): 5962-9. [PMID:14522923]

4. French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. (2010) Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J. Pharmacol. Exp. Ther., 333 (1): 129-39. [PMID:20061445]

5. Paugh SW, Paugh BS, Rahmani M, Kapitonov D, Almenara JA, Kordula T, Milstien S, Adams JK, Zipkin RE, Grant S et al.. (2008) A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia. Blood, 112 (4): 1382-91. [PMID:18511810]

6. Pitman MR, Powell JA, Coolen C, Moretti PA, Zebol JR, Pham DH, Finnie JW, Don AS, Ebert LM, Bonder CS et al.. (2015) A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties. Oncotarget, 6 (9): 7065-83. [PMID:25788259]

7. Schnute ME, McReynolds MD, Carroll J, Chrencik J, Highkin MK, Iyanar K, Jerome G, Rains JW, Saabye M, Scholten JA et al.. (2017) Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits. J. Med. Chem., 60 (6): 2562-2572. [PMID:28231433]

8. Schnute ME, McReynolds MD, Kasten T, Yates M, Jerome G, Rains JW, Hall T, Chrencik J, Kraus M, Cronin CN et al.. (2012) Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem. J., 444 (1): 79-88. [PMID:22397330]

9. Sibley CD, Morris EA, Kharel Y, Brown AM, Huang T, Bevan DR, Lynch KR, Santos WL. (2020) Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity. J. Med. Chem., 63 (3): 1178-1198. [PMID:31895563]

How to cite this page