Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT618Q2)

DTT Name	Sphingosine-1-phosphate lyase 1 (SGPL1)
Synonyms	hSPL; Sphingosine-1-phosphate aldolase; SPL 1; SP-lyase 1; S1PL; KIAA1252
Gene Name	SGPL1
DTT Type	Clinical trial target	[1]
BioChemical Class	Carbon-carbon lyase
UniProt ID	SGPL1_HUMAN
TTD ID	T01575
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 4.1.2.27
Sequence	MPSTDLLMLKAFEPYLEILEVYSTKAKNYVNGHCTKYEPWQLIAWSVVWTLLIVWGYEFV FQPESLWSRFKKKCFKLTRKMPIIGRKIQDKLNKTKDDISKNMSFLKVDKEYVKALPSQG LSSSAVLEKLKEYSSMDAFWQEGRASGTVYSGEEKLTELLVKAYGDFAWSNPLHPDIFPG LRKIEAEIVRIACSLFNGGPDSCGCVTSGGTESILMACKAYRDLAFEKGIKTPEIVAPQS AHAAFNKAASYFGMKIVRVPLTKMMEVDVRAMRRAISRNTAMLVCSTPQFPHGVIDPVPE VAKLAVKYKIPLHVDACLGGFLIVFMEKAGYPLEHPFDFRVKGVTSISADTHKYGYAPKG SSLVLYSDKKYRNYQFFVDTDWQGGIYASPTIAGSRPGGISAACWAALMHFGENGYVEAT KQIIKTARFLKSELENIKGIFVFGNPQLSVIALGSRDFDIYRLSNLMTAKGWNLNQLQFP PSIHFCITLLHARKRVAIQFLKDIRESVTQIMKNPKAKTTGMGAIYGMAQTTVDRNMVAE LSSVFLDSLYSTDTVTQGSQMNGSPKPH
Function	Elevates stress-induced ceramide production and apoptosis. Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP. Seems to play a role in establishing neuronal contact sites and axonal maintenance. Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine.
KEGG Pathway	Sphingolipid metabolism (hsa00600 ) Metabolic pathways (hsa01100 ) Sphingolipid signaling pathway (hsa04071 )
Reactome Pathway	Sphingolipid de novo biosynthesis (R-HSA-1660661 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

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1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LX2931	DMLA8H3	Hereditary acantholytic dermatoses	EC20.2	Phase 2	[1]
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1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LX-2932	DMMRLPF	Autoimmune diabetes	5A10	Terminated	[2]
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1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID24809814C31	DMI8T1Y	Discovery agent	N.A.	Investigative	[3]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	1.63E-02	0.38	0.9
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References

1	Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702.
2	Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932). J Med Chem. 2010 Dec 23;53(24):8650-62.
3	Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis. J MedChem. 2014 Jun 26;57(12):5074-84.