Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCN0M9)

• DTT Name: Sphingosine kinase 2 (SPHK2)
• Synonyms: SPK 2; SK 2
• Gene Name: SPHK2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: SPHK2_HUMAN
• TTD ID: T31989
• EC Number: EC 2.7.1.91
• Sequence:
  MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPA
  RGPRFALTLTSQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTY
  PRGRRGARRRATRTFRADGAATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRP
  PRLLLLVNPFGGRGLAWQWCKNHVLPMISEAGLSFNLIQTERQNHARELVQGLSLSEWDG
  IVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGNALAGAVNQHGGFEPALGLDL
  LLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERFRALGSARFTL
  GTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSV
  SDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKA
  ALHSPVSEGAPVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVL
  MLAISPSHLGADLVAAPHARFDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQL
  GYAAARAFRLEPLTPRGVLTVDGEQVEYGPLQAQMHPGIGTLLTGPPGCPGREP
• Function: Acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides. Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
  Calcium signaling pathway (hsa04020)
  Sphingolipid signaling pathway (hsa04071)
  VEGF signaling pathway (hsa04370)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Tuberculosis (hsa05152)
• Reactome Pathway: Sphingolipid de novo biosynthesis (R-HSA-1660661)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABC294640	DMCKPG4	Advanced solid tumour	2A00-2F9Z	Phase 3	[1]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-2-amino-3-(4-octylphenylamino)propan-1-ol	DMZXT34	Discovery agent	N.A.	Investigative	[2]
(R)-2-amino-4-hydroxy-N-(4-octylphenyl)butanamide	DMA1EFL	Discovery agent	N.A.	Investigative	[2]
(S)-2-amino-4-hydroxy-N-(4-octylphenyl)butanamide	DM8A1HG	Discovery agent	N.A.	Investigative	[2]
(S)-2-amino-6-hydroxy-N-(4-octylphenyl)hexanamide	DMG0CSZ	Discovery agent	N.A.	Investigative	[2]
DIMETHYLSPINGOSINE	DM1OKN0	N. A.	N. A.	Investigative	[3]
ROMe	DMAROW1	Discovery agent	N.A.	Investigative	[4]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Sphingosine kinase 2 (SPHK2) DME Info
• Gene Name: SPHK2

1 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sphingosine-1-phosphate	DMJCQKA	Acne vulgaris	ED80	Phase 1	[5]

References

• [1] Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702.
• [2] Discovery of novel sphingosine kinase 1 inhibitors. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6119-21.
• [3] Synthesis and evaluation of sphingosine analogues as inhibitors of sphingosine kinases. J Med Chem. 2009 Jun 25;52(12):3618-26.
• [4] (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. 2011 Oct;23(10):1590-5.
• [5] Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases. J Biol Chem. 2003 Nov 28;278(48):47408-15.