Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T01575
(Former ID: TTDI02173)
|
|||||
| Target Name |
Sphingosine-1-phosphate lyase 1 (SGPL1)
|
|||||
| Synonyms |
hSPL; Sphingosine-1-phosphate aldolase; SPL 1; SP-lyase 1; S1PL; KIAA1252
|
|||||
| Gene Name |
SGPL1
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Congenital ichthyosis [ICD-11: EC20] | |||||
| 2 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| 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.
Click to Show/Hide
|
|||||
| BioChemical Class |
Carbon-carbon lyase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 4.1.2.27
|
|||||
| Sequence |
MPSTDLLMLKAFEPYLEILEVYSTKAKNYVNGHCTKYEPWQLIAWSVVWTLLIVWGYEFV
FQPESLWSRFKKKCFKLTRKMPIIGRKIQDKLNKTKDDISKNMSFLKVDKEYVKALPSQG LSSSAVLEKLKEYSSMDAFWQEGRASGTVYSGEEKLTELLVKAYGDFAWSNPLHPDIFPG LRKIEAEIVRIACSLFNGGPDSCGCVTSGGTESILMACKAYRDLAFEKGIKTPEIVAPQS AHAAFNKAASYFGMKIVRVPLTKMMEVDVRAMRRAISRNTAMLVCSTPQFPHGVIDPVPE VAKLAVKYKIPLHVDACLGGFLIVFMEKAGYPLEHPFDFRVKGVTSISADTHKYGYAPKG SSLVLYSDKKYRNYQFFVDTDWQGGIYASPTIAGSRPGGISAACWAALMHFGENGYVEAT KQIIKTARFLKSELENIKGIFVFGNPQLSVIALGSRDFDIYRLSNLMTAKGWNLNQLQFP PSIHFCITLLHARKRVAIQFLKDIRESVTQIMKNPKAKTTGMGAIYGMAQTTVDRNMVAE LSSVFLDSLYSTDTVTQGSQMNGSPKPH Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | LX2931 | Drug Info | Phase 2 | Rheumatoid arthritis | [2] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | LX-2932 | Drug Info | Terminated | Autoimmune diabetes | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | LX2931 | Drug Info | [1], [4] | |||
| 2 | LX-2932 | Drug Info | [5] | |||
| 3 | PMID24809814C31 | Drug Info | [6] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Sphingolipid metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Sphingolipid signaling pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Sphingolipid Metabolism | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Sphingosine 1-phosphate (S1P) pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Sphingolipid de novo biosynthesis | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Sphingolipid metabolism | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702. | |||||
| REF 2 | ClinicalTrials.gov (NCT00903383) Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate. U.S. National Institutes of Health. | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021957) | |||||
| REF 4 | S1P is associated with protection in human and experimental cerebral malaria. Mol Med. 2011;17(7-8):717-25. | |||||
| REF 5 | 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. | |||||
| REF 6 | 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. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.