Top ▲
Target has curated data in GtoImmuPdb
Target id: 2204
Nomenclature: sphingosine kinase 1
Abbreviated Name: SPHK1
Family: Sphingosine kinase
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 384 | 17q25.1 | SPHK1 | sphingosine kinase 1 | |
Mouse | - | 382 | 11 E2 | Sphk1 | sphingosine kinase 1 | |
Rat | - | 383 | 10q32.1-q32.2 | Sphk1 | sphingosine kinase 1 |
Previous and Unofficial Names |
SK1 | SPHK |
Database Links | |
Alphafold | Q9NYA1 (Hs), Q8CI15 (Mm), Q91V26 (Rn) |
BRENDA | 2.7.1.91 |
CATH/Gene3D | 3.40.50.10330 |
ChEMBL Target | CHEMBL4394 (Hs), CHEMBL2401605 (Mm), CHEMBL1075107 (Rn) |
Ensembl Gene | ENSG00000176170 (Hs), ENSMUSG00000061878 (Mm), ENSRNOG00000010626 (Rn) |
Entrez Gene | 8877 (Hs), 20698 (Mm), 170897 (Rn) |
Human Protein Atlas | ENSG00000176170 (Hs) |
KEGG Enzyme | 2.7.1.91 |
KEGG Gene | hsa:8877 (Hs), mmu:20698 (Mm), rno:170897 (Rn) |
OMIM | 603730 (Hs) |
Pharos | Q9NYA1 (Hs) |
RefSeq Nucleotide | NM_001142601 (Hs), NM_001172472 (Mm), NM_133386 (Rn) |
RefSeq Protein | NP_001136073 (Hs), NP_001165943 (Mm), NP_596877 (Rn) |
SynPHARM | 78563 (in complex with PF-543) |
UniProtKB | Q9NYA1 (Hs), Q8CI15 (Mm), Q91V26 (Rn) |
Wikipedia | SPHK1 (Hs) |
Enzyme Reaction | ||||
|
Cofactors | ||||||||
|
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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Immunopharmacology Comments |
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK1-selective inhibitors include PF-543 [7-8]. Dual SK1/SK2 inhibitors include SLC4011540 [2], Compound 49 [1], MP-A08 [6] and SKI-II [4]. |
Immuno Process Associations | ||
|
||
|
||
|
||
|
||
|
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]
10. Zhang S, Chen X, Wu C, Xu H, Xie X, Feng M, Hu S, Bai H, Gao F, Tong L et al.. (2022) Novel Sphingosine Kinase 1 Inhibitor Suppresses Growth of Solid Tumor and Inhibits the Lung Metastasis of Triple-Negative Breast Cancer. J Med Chem, 65 (11): 7697-7716. [PMID:35439002]