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Target has curated data in GtoImmuPdb
Target id: 2205
Nomenclature: sphingosine kinase 2
Abbreviated Name: SPHK2
Family: Sphingosine kinase
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 654 | 19q13.33 | SPHK2 | sphingosine kinase 2 | |
Mouse | - | 617 | 7 B3 | Sphk2 | sphingosine kinase 2 | |
Rat | - | 616 | 1q22 | Sphk2 | sphingosine kinase 2 |
Previous and Unofficial Names |
SK2 |
Database Links | |
Alphafold | Q9NRA0 (Hs), Q9JIA7 (Mm), Q6AYB2 (Rn) |
BRENDA | 2.7.1.91 |
CATH/Gene3D | 3.40.50.10330 |
ChEMBL Target | CHEMBL3023 (Hs), CHEMBL1075305 (Mm), CHEMBL1075197 (Rn) |
Ensembl Gene | ENSG00000063176 (Hs), ENSMUSG00000057342 (Mm), ENSRNOG00000021032 (Rn) |
Entrez Gene | 56848 (Hs), 56632 (Mm), 308589 (Rn) |
Human Protein Atlas | ENSG00000063176 (Hs) |
KEGG Enzyme | 2.7.1.91 |
KEGG Gene | hsa:56848 (Hs), mmu:56632 (Mm), rno:308589 (Rn) |
OMIM | 607092 (Hs) |
Pharos | Q9NRA0 (Hs) |
RefSeq Nucleotide | NM_001204158 (Hs), NM_001172561 (Mm), NM_001012066 (Rn) |
RefSeq Protein | NP_064511 (Hs), NP_001166032 (Mm), NP_001012066 (Rn) |
UniProtKB | Q9NRA0 (Hs), Q9JIA7 (Mm), Q6AYB2 (Rn) |
Wikipedia | SPHK2 (Hs) |
Enzyme Reaction | ||||
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Cofactors | ||||||||
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling, and is considered to be an anti-inflammatory enzyme with potential druggability for the treatment of autoimmune and inflammatory diseases [7]. Selective SK2 inhibitors are being used to explore the feasibility of targeting SK2 [8]. SK-2-selective inhibitors include Compound 27d [9], Compound 55, Compound 59, Compound 60 [1], SLM6071469 [10] and SLC4101431 [2]. Dual SK1/SK2 inhibitors include SLC4011540 [2], Compound 49 [1], MP-A08 [6] and SKI-II [3]. In 2020, in reponse to the SARS-CoV-2 pandemic, the SK2 inhibitor opaganib was evaluated (on compassionate grounds see NCT04435106) in patients with severe COVID-19 and hyperinflammation. Results have not yet been published but are available via the medRxiv preprint server (Kurd et al., Compassionate Use of Opaganib For Patients with Severe COVID-19; doi.org/10.1101/2020.06.20.20099010). Phase 2 study NCT04414618 was recruiting as of 23 June 2020. |
Immuno Process Associations | ||
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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, 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. Gao P, Peterson YK, Smith RA, Smith CD. (2012) Characterization of isoenzyme-selective inhibitors of human sphingosine kinases. PLoS ONE, 7 (9): e44543. [PMID:22970244]
5. Lim KG, Sun C, Bittman R, Pyne NJ, Pyne S. (2011) (R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect on sphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells. Cell Signal, 23 (10): 1590-5. [PMID:21620961]
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. Pyne NJ, Adams DR, Pyne S. (2017) Sphingosine Kinase 2 in Autoimmune/Inflammatory Disease and the Development of Sphingosine Kinase 2 Inhibitors. Trends Pharmacol Sci, 38 (7): 581-591. [PMID:28606480]
8. Pyne S, Adams DR, Pyne NJ. (2020) Sphingosine Kinases as Druggable Targets. Handb Exp Pharmacol, 259: 49-76. [PMID:29460151]
9. 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]
10. 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]