sphingosine kinase 1 | Sphingosine kinase | IUPHAR/BPS Guide to PHARMACOLOGY

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sphingosine kinase 1

Target not currently curated in GtoImmuPdb

Target id: 2204

Nomenclature: sphingosine kinase 1

Abbreviated Name: SPHK1

Family: Sphingosine kinase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
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
SK1 | SPHK
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.1.91 Sphingosine + ATP = sphingosine 1-phosphate + ADP
dihydrosphingosine + ATP = sphingosine 1-phosphate + ADP
Cofactors
Cofactor Species Comments Reference
Mg2+ None

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF-543 Hs Inhibition 8.4 pKi 7
pKi 8.4 (Ki 3.6x10-9 M) [7]
SLC4101431 Hs Inhibition 5.1 pKi 1
pKi 5.1 (Ki 9x10-6 M) [1]
SKI II Hs Inhibition 4.8 pKi 3
pKi 4.8 (Ki 1.6x10-5 M) [3]
PF-543 Hs Inhibition 8.6 – 8.7 pIC50 6-7
pIC50 8.7 (IC50 2x10-9 M) [7]
pIC50 8.6 (IC50 2.7x10-9 M) [6]
SKI II Hs Inhibition 6.3 pIC50 2
pIC50 6.3 (IC50 5x10-7 M) [2]
Description: Measured using a GST-hSPHK1 fusion protein
compound 27d [PMID: 28231433] Hs Inhibition 5.0 pIC50 6
pIC50 5.0 (IC50 9.82x10-6 M) [6]
MP-A08 Hs Inhibition 4.6 pIC50 5
pIC50 4.6 (IC50 2.7x10-5 M) [5]
Description: In vitro inhibition of substrate phosphorylation.
SK1-I Hs Inhibition - - 4
[4]

References

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1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

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