Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.1.91 extracted from

  • Patwardhan, N.N.; Morris, E.A.; Kharel, Y.; Raje, M.R.; Gao, M.; Tomsig, J.L.; Lynch, K.R.; Santos, W.L.
    Structure-activity relationship studies and in vivo activity of guanidine-based sphingosine kinase inhibitors: discovery of SphK1- and SphK2-selective inhibitors (2015), J. Med. Chem., 58, 1879-1899.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.1.91

Inhibitors

Inhibitors Comment Organism Structure
(R)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide
-
 Homo sapiens
(R)-amino(2-((4-decylphenyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate
-
 Homo sapiens
(R)-amino(3-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-pyrrolidin-1-yl)methaniminium
-
 Homo sapiens
(R)-FTY720-OMe
-
 Homo sapiens
(S)-1-(1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)-guanidine
-
 Homo sapiens
(S)-1-(2-methyl-1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-propyl)guanidine
-
 Homo sapiens
(S)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboximidamide
-
 Homo sapiens
(S)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide
-
 Homo sapiens
(S)-2-(5-(4-octylphenyl)-1,3,4-oxadiazol-2-yl)pyrrolidin-1-ium 2,2,2-trifluoroacetate
-
 Homo sapiens
(S)-amino((2-hydroxy-1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)methaniminium
-
 Homo sapiens
(S)-amino(2-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-methyl)pyrrolidin-1-yl)methaniminium chloride
-
 Homo sapiens
(S)-amino(2-((4-decylphenyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate
-
 Homo sapiens
(S)-amino(2-((4-octylbenzamido)methyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate
-
 Homo sapiens
(S)-amino(2-((4-octylbenzyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate
-
 Homo sapiens
(S)-amino(2-(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-ethyl)pyrrolidin-1-yl)methaniminium
-
 Homo sapiens
(S)-amino(2-(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-ethyl)pyrrolidin-1-yl)methaniminium chloride
-
 Homo sapiens
(S)-amino(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-2,5-di-hydro-1H-pyrrol-1-yl)methaniminium 2,2,2-trifluoroacetate
-
 Homo sapiens
(S)-amino(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl)methaniminium
-
 Homo sapiens
(S)-amino(2-(5-(4-octylphenyl)-1,2,4-oxadiazol-3-yl)-pyrrolidin-1-yl)methaniminium
-
 Homo sapiens
1-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)guanidine
-
 Homo sapiens
1-(1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)cyclopropyl)-guanidine
-
 Homo sapiens
1-methyl-1-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)-guanidine
-
 Homo sapiens
2-(hydroxymethyl)-1-[2-[4-([4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]amino)phenyl]ethyl]piperidin-4-ol a dual SphK1/2 inhibitor; a dual SphK1/2 inhibitor Homo sapiens
4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol
-
 Homo sapiens
ABC294640
-
 Homo sapiens
amino((1S,3S)-3-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium
-
 Homo sapiens
amino((1S,4S)-4-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium
-
 Homo sapiens
amino((2S,4R)-4-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium
-
 Homo sapiens
amino(3-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methaniminium
-
 Homo sapiens
compound 51
-
 Homo sapiens
dimethylsphingosine
-
 Homo sapiens
additional information structure-activity relationship studies and in vivo activity of guanidine-based sphingosine kinase inhibitors, SphK1- and SphK2-selective inhibitors, discovery of selective, nanomolar inhibitors, chemical synthesis, overview; structure-activity relationship studies and in vivo activity of guanidine-based sphingosine kinase inhibitors, SphK1- and SphK2-selective inhibitors, discovery of selective, nanomolar inhibitors, chemical synthesis, overview Homo sapiens
PF-543
-
 Homo sapiens
SKI-II
-
 Homo sapiens
SLR080811
-
 Homo sapiens
VPC96091
-
 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm isozyme SphK1 is mostly in the cytoplasm and migrates to the plasma membrane upon phosphorylation Homo sapiens 5737
-
nucleus isozyme SphK2 localizes in the nucleus Homo sapiens 5634
-
plasma membrane isozyme SphK1 is mostly in the cytoplasm and migrates to the plasma membrane upon phosphorylation Homo sapiens 5886
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + sphingosine Homo sapiens
-
 ADP + sphingosine 1-phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NRA0 sphingosine kinase isoform 2
-
Homo sapiens Q9NYA1 sphingosine kinase isoform 1
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein isozyme SphK1 migrates to the plasma membrane upon phosphorylation Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
U-937 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + sphingosine
-
 Homo sapiens ADP + sphingosine 1-phosphate
-
 ?

Synonyms

Synonyms Comment Organism
sphingosine kinase 1
-
 Homo sapiens
sphingosine kinase 2
-
 Homo sapiens
SPHK1
-
 Homo sapiens
SPHK2
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.012
-
 (S)-amino(2-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-methyl)pyrrolidin-1-yl)methaniminium chloride pH and temperature not specified in the publication Homo sapiens
0.042
-
 (S)-2-(5-(4-octylphenyl)-1,3,4-oxadiazol-2-yl)pyrrolidin-1-ium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.044
-
 (R)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide pH and temperature not specified in the publication Homo sapiens
0.056
-
 (S)-amino(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.065
-
 amino((2S,4R)-4-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.069
-
 amino((1S,3S)-3-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.07
-
 (S)-1-(2-methyl-1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-propyl)guanidine pH and temperature not specified in the publication Homo sapiens
0.07
-
 amino((1S,4S)-4-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.075
-
 1-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)guanidine pH and temperature not specified in the publication Homo sapiens
0.075
-
 (S)-amino(2-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-methyl)pyrrolidin-1-yl)methaniminium chloride pH and temperature not specified in the publication Homo sapiens
0.077
-
 (S)-amino(2-(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-ethyl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.078
-
 (S)-1-(1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)-guanidine pH and temperature not specified in the publication Homo sapiens
0.08
-
 (S)-amino(2-(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-ethyl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.083
-
 (R)-amino(2-((4-decylphenyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.084
-
 amino(3-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.085
-
 (S)-amino((2-hydroxy-1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)methaniminium pH and temperature not specified in the publication Homo sapiens
0.088
-
 1-(1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)cyclopropyl)-guanidine pH and temperature not specified in the publication Homo sapiens
0.088
-
 (S)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide pH and temperature not specified in the publication Homo sapiens
0.088
-
 (R)-amino(3-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.09
-
 1-methyl-1-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)-guanidine pH and temperature not specified in the publication Homo sapiens
0.09
-
 (S)-1-(1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)-guanidine pH and temperature not specified in the publication Homo sapiens
0.09
-
 (S)-amino(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-2,5-di-hydro-1H-pyrrol-1-yl)methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.09
-
 amino(3-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)azetidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.09
-
 (S)-amino(2-((4-octylbenzamido)methyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.091
-
 (S)-amino(2-(5-(4-octylphenyl)-1,2,4-oxadiazol-3-yl)-pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.091
-
 (S)-amino(2-((4-decylphenyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.092
-
 (S)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboximidamide pH and temperature not specified in the publication Homo sapiens
0.092
-
 amino((1S,3S)-3-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.093
-
 (R)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide pH and temperature not specified in the publication Homo sapiens
0.094
-
 (S)-1-(2-methyl-1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-propyl)guanidine pH and temperature not specified in the publication Homo sapiens
0.094
-
 (S)-amino((2-hydroxy-1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)amino)methaniminium pH and temperature not specified in the publication Homo sapiens
0.094
-
 (S)-amino(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-2,5-di-hydro-1H-pyrrol-1-yl)methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.095
-
 (S)-amino(2-(5-(4-octylphenyl)-1,2,4-oxadiazol-3-yl)-pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.095
-
 (S)-amino(2-((4-octylbenzyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.095
-
 (S)-amino(2-((4-octylbenzamido)methyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.096
-
 (S)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboximidamide pH and temperature not specified in the publication Homo sapiens
0.096
-
 amino((1S,4S)-4-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.096
-
 (R)-amino(3-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.096
-
 (S)-2-(5-(4-octylphenyl)-1,3,4-oxadiazol-2-yl)pyrrolidin-1-ium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.098
-
 1-methyl-1-((3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)methyl)-guanidine pH and temperature not specified in the publication Homo sapiens
0.098
-
 (S)-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide pH and temperature not specified in the publication Homo sapiens
0.098
-
 (S)-amino(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.098
-
 amino((2S,4R)-4-hydroxy-2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl)methaniminium pH and temperature not specified in the publication Homo sapiens
0.099
-
 1-(1-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)cyclopropyl)-guanidine pH and temperature not specified in the publication Homo sapiens
0.1
-
 (S)-amino(2-(2-(3-(4-octylphenyl)-1,2,4-oxadiazol-5-yl)-ethyl)pyrrolidin-1-yl)methaniminium chloride pH and temperature not specified in the publication Homo sapiens
0.1
-
 (S)-amino(2-((4-decylphenyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.1
-
 (R)-amino(2-((4-decylphenyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens
0.1
-
 (S)-amino(2-((4-octylbenzyl)carbamoyl)pyrrolidin-1-yl)-methaniminium 2,2,2-trifluoroacetate pH and temperature not specified in the publication Homo sapiens

General Information

General Information Comment Organism
physiological function sphingosine 1-phosphate is a pleiotropic signaling molecule that acts as a ligand for five G-protein coupled receptors (S1P1-5) whose downstream effects are implicated in a variety of important pathologies including sickle cell disease, cancer, inflammation, and fibrosis. The synthesis of S1P is catalyzed by sphingosine kinase (SphK) isoforms 1 and 2 Homo sapiens
physiological function sphingosine 1-phosphate is a pleiotropic signaling molecule that acts as a ligand for five G-protein coupled receptors (S1P1-5) whose downstream effects are implicated in a variety of important pathologies including sickle cell disease, cancer, inflammation, and fibrosis. The synthesis of S1P is catalyzed by sphingosine kinase (SphK) isoforms 1 and 2. Isozyme SphK2 can localize in the nucleus to inhibit DNA synthesis and regulate HDAC1/2 activity Homo sapiens