Target Information

Target General Infomation
Target ID
T01575
Former ID
TTDI02173
Target Name
Sphingosine 1 phosphate lyase 1
Gene Name
SGPL1
Synonyms
S1PL; SP-lyase 1; SPL 1; Sphingosine-1-phosphate aldolase; hSPL; SGPL1
Target Type
Clinical Trial
Disease Autoimmune diabetes [ICD10: E08-E13]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis.
BioChemical Class
Carbon-carbon lyase
UniProt ID
O95470
EC Number
EC 4.1.2.27
Sequence
MPSTDLLMLKAFEPYLEILEVYSTKAKNYVNGHCTKYEPWQLIAWSVVWTLLIVWGYEFV
FQPESLWSRFKKKCFKLTRKMPIIGRKIQDKLNKTKDDISKNMSFLKVDKEYVKALPSQG
LSSSAVLEKLKEYSSMDAFWQEGRASGTVYSGEEKLTELLVKAYGDFAWSNPLHPDIFPG
LRKIEAEIVRIACSLFNGGPDSCGCVTSGGTESILMACKAYRDLAFEKGIKTPEIVAPQS
AHAAFNKAASYFGMKIVRVPLTKMMEVDVRAMRRAISRNTAMLVCSTPQFPHGVIDPVPE
VAKLAVKYKIPLHVDACLGGFLIVFMEKAGYPLEHPFDFRVKGVTSISADTHKYGYAPKG
SSLVLYSDKKYRNYQFFVDTDWQGGIYASPTIAGSRPGGISAACWAALMHFGENGYVEAT
KQIIKTARFLKSELENIKGIFVFGNPQLSVIALGSRDFDIYRLSNLMTAKGWNLNQLQFP
PSIHFCITLLHARKRVAIQFLKDIRESVTQIMKNPKAKTTGMGAIYGMAQTTVDRNMVAE
LSSVFLDSLYSTDTVTQGSQMNGSPKPH
Drugs and Mode of Action
Drug(s) LX2931 Drug Info Phase 2 Rheumatoid arthritis [522666]
LX-2932 Drug Info Terminated Autoimmune diabetes [548103]
Inhibitor compound 31 Drug Info [532772]
LX-2932 Drug Info [531269]
LX2931 Drug Info [531468], [532456]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Sphingolipid metabolism
Metabolic pathways
Sphingolipid signaling pathway
Pathway Interaction Database Sphingosine 1-phosphate (S1P) pathway
PathWhiz Pathway Sphingolipid Metabolism
Reactome Sphingolipid de novo biosynthesis
WikiPathways Sphingolipid metabolism
References
Ref 522666ClinicalTrials.gov (NCT00903383) Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate. U.S. National Institutes of Health.
Ref 548103Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021957)
Ref 531269Inhibition 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.
Ref 531468S1P is associated with protection in human and experimental cerebral malaria. Mol Med. 2011;17(7-8):717-25.
Ref 532456Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702.
Ref 532772Orally 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.

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