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Literature summary for 2.7.1.91 extracted from

  • Sibley, C.D.; Morris, E.A.; Kharel, Y.; Brown, A.M.; Huang, T.; Bevan, D.R.; Lynch, K.R.; Santos, W.L.
    Discovery of a small side cavity in sphingosine kinase 2 that enhances inhibitor potency and selectivity (2020), J. Med. Chem., 63, 1178-1198 .
    View publication on PubMed
Search for more literature for 2.7.1.91

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Saccharomyces cerevisiae strain KYA1 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2S)-2-[3-[4-(octyloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide SLM6031434, the inhibitor is 23fold selective for isoform SphK2 over SphK1 with 51% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(2S)-2-[3-[4-(octyloxy)phenyl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide 8% inhibition of isoform SphK2 at 0.001 mM Homo sapiens
(S)-2-(3-(2-(trifluoromethyl)-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 35% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(2-chloro-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 40% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3,5-dimethyl-4-((4-(trifluoromethyl)benzyl)-oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 23% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-(pyridin-4-yl)-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 8% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-(tert-butyl)-4-((4-(trifluoromethyl)benzyl)-oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 66% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-(trifluoromethyl)-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide SLM6071469, the inhibitor is 73fold selective for isoform SphK2 over SphK1 with 65% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-allyl-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 59% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-bromo-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 24% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-chloro-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 33% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-cyclopropyl-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 52% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-ethyl-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 42% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-fluoro-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 23% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-isopropyl-4-((4-(trifluoromethyl)benzyl)-oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 67% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-methoxy-4-((4-(trifluoromethyl)benzyl)-oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 15% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-methyl-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 3% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-nitro-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 33% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(3-propyl-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 60% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(4'-fluoro-6-((4-(trifluoromethyl)benzyl)oxy)-[1,1'-biphenyl]-3-yl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 31% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(4-((4-(trifluoromethyl)benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 2% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(4?-(trifluoromethyl)-6-((4-(trifluoromethyl)-benzyl)oxy)-[1,1'-biphenyl]-3-yl)-1,2,4-oxadiazol-5-yl)-pyrrolidine-1-carboximidamide 12% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
(S)-2-(3-(6-((4-(trifluoromethyl)benzyl)oxy)-[1,1'-biphenyl]-3-yl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide 28% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
Amgen 23
-
 Homo sapiens
fingolimod
-
 Homo sapiens
MP-A08
-
 Homo sapiens
PF-543
-
 Homo sapiens
siponimod
-
 Homo sapiens
SLM6031434 the inhibitor is 23fold selective for isoform SphK2 over SphK1 with 51% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
SLM6071469 i.e. (S)-2-(3-(3-(trifluoromethyl)-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide. The inhibitor is 73fold selective for isoform SphK2 over SphK1 with 65% inhibition of isoform SphK2 at 0.0003 mM Homo sapiens
SLP7111228
-
 Homo sapiens
SLR080811
-
 Homo sapiens
[(2R)-1-([4-[(3-cyclohexylphenoxy)methyl]phenyl]methyl)pyrrolidin-2-yl]methanol
-
 Homo sapiens

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
-
 ir

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NRA0
-
-

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
sphingosine kinase 2
-
 Homo sapiens
SPHK2 isoform Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000089
-
 (S)-2-(3-(3-(trifluoromethyl)-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.000089
-
 SLM6071469 isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.000186
-
 (S)-2-(3-(3-cyclopropyl-4-((4-(trifluoromethyl)-benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.000192
-
 (S)-2-(3-(3-isopropyl-4-((4-(trifluoromethyl)benzyl)-oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.000197
-
 (S)-2-(3-(3-(tert-butyl)-4-((4-(trifluoromethyl)benzyl)-oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.000201
-
 (S)-2-(3-(3-propyl-4-((4-(trifluoromethyl)benzyl)oxy)-phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.00037
-
 (2S)-2-[3-[4-(octyloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboximidamide isoform SphK2, at pH 8.0 and 25°C Homo sapiens
0.00037
-
 SLM6031434 isoform SphK2, at pH 8.0 and 25°C Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000017
-
 IC50 below 0.0000017 mM, isoform SphK2, at pH 8.0 and 25°C Homo sapiens [(2R)-1-([4-[(3-cyclohexylphenoxy)methyl]phenyl]methyl)pyrrolidin-2-yl]methanol