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Literature summary extracted from

  • Weiler, S.; Braendlin, N.; Beerli, C.; Bergsdorf, C.; Schubart, A.; Srinivas, H.; Oberhauser, B.; Billich, A.
    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 (2014), J. Med. Chem., 57, 5074-5084 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
4.1.2.27 expressed in Sf9 insect cells Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
4.1.2.27 in complex with (R)-6-(4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile, hanging drop vapor diffusion method Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
4.1.2.27 (R)-1-benzyl-4-(3-methyl-4-(5-(trifluoromethyl)pyridin-2-yl)-piperazin-1-yl)phthalazine
-
 Homo sapiens
4.1.2.27 (R)-1-benzyl-4-(3-methyl-4-(5-nitropyridin-2-yl)piperazin-1-yl)-phthalazine
-
 Homo sapiens
4.1.2.27 (R)-1-benzyl-4-(4-(5-cyanopyridin-2-yl)-3-methylpiperazin-1-yl)phthalazine-6-carbonitrile
-
 Homo sapiens
4.1.2.27 (R)-4-benzyl-1-(4-(5-cyanopyridin-2-yl)-3-methylpiperazin-1-yl)phthalazine-6-carbonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(2-methyl-4-(4-phenethylphthalazin-1-yl)piperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(2-methyl-4-(4-phenylphthalazin-1-yl)piperazin-1-yl)-nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzyl-6-(trifluoromethyl)phthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzyl-6-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzyl-7-(trifluoromethyl)phthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzylphthalazin-1-yl)-2-ethylpiperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzylphthalazin-1-yl)-2-isopropylpiperazin-1-yl)-nicotinonitrile
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl)-nicotinic acid
-
 Homo sapiens
4.1.2.27 (R)-6-(4-(4-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)-nicotinonitrile
-
 Homo sapiens
4.1.2.27 (S)-6-(4-(4-benzylphthalazin-1-yl)-2-(hydroxymethyl)piperazin-1-yl)nicotinonitrile
-
 Homo sapiens
4.1.2.27 2-acetyl-4-tetrahydroxybutylimidazole
-
 Homo sapiens
4.1.2.27 6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile
-
 Homo sapiens
4.1.2.27 6-[4-(4-benzylphthalazin-1-yl)piperazin-1-yl]pyridine-3-carbonitrile
-
 Homo sapiens
4.1.2.27 deoxypyridoxine
-
 Homo sapiens
4.1.2.27 ethyl 6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carboxylate
-
 Homo sapiens
4.1.2.27 FTY720
-
 Homo sapiens
4.1.2.27 LX2931
-
 Homo sapiens
4.1.2.27 [(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.1.2.27 sphinganine 1-phosphate Homo sapiens
-
 phosphoethanolamine + palmitaldehyde
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
4.1.2.27 Homo sapiens O95470
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
4.1.2.27 Ni-NTA column chromatography and Superdex 200 gel filtration Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.1.2.27 sphinganine 1-phosphate
-
 Homo sapiens phosphoethanolamine + palmitaldehyde
-
 ?

Subunits

EC Number Subunits Comment Organism
4.1.2.27 homodimer
-
 Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
4.1.2.27 S1P lyase
-
 Homo sapiens
4.1.2.27 S1PL
-
 Homo sapiens
4.1.2.27 sphingosine 1-phosphate lyase
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
4.1.2.27 0.000024
-
 at pH 7.4 and 25°C Homo sapiens (R)-1-benzyl-4-(4-(5-cyanopyridin-2-yl)-3-methylpiperazin-1-yl)phthalazine-6-carbonitrile
4.1.2.27 0.0001
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzyl-7-(trifluoromethyl)phthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
4.1.2.27 0.00021
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
4.1.2.27 0.00074
-
 at pH 7.4 and 25°C Homo sapiens (R)-1-benzyl-4-(3-methyl-4-(5-nitropyridin-2-yl)piperazin-1-yl)-phthalazine
4.1.2.27 0.0013
-
 at pH 7.4 and 25°C Homo sapiens (R)-4-benzyl-1-(4-(5-cyanopyridin-2-yl)-3-methylpiperazin-1-yl)phthalazine-6-carbonitrile
4.1.2.27 0.0017
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzylphthalazin-1-yl)-2-ethylpiperazin-1-yl)nicotinonitrile
4.1.2.27 0.0023
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzyl-6-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
4.1.2.27 0.0024
-
 at pH 7.4 and 25°C Homo sapiens 6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile
4.1.2.27 0.0025
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzylphthalazin-1-yl)-2-isopropylpiperazin-1-yl)-nicotinonitrile
4.1.2.27 0.0034
-
 at pH 7.4 and 25°C Homo sapiens ethyl 6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carboxylate
4.1.2.27 0.012
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzyl-6-(trifluoromethyl)phthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile
4.1.2.27 0.03
-
 at pH 7.4 and 25°C Homo sapiens (R)-1-benzyl-4-(3-methyl-4-(5-(trifluoromethyl)pyridin-2-yl)-piperazin-1-yl)phthalazine
4.1.2.27 0.03
-
 at pH 7.4 and 25°C Homo sapiens (R)-6-(2-methyl-4-(4-phenethylphthalazin-1-yl)piperazin-1-yl)nicotinonitrile
4.1.2.27 0.03
-
 IC50 above 0.03 mM, at pH 7.4 and 25°C Homo sapiens (R)-6-(2-methyl-4-(4-phenylphthalazin-1-yl)piperazin-1-yl)-nicotinonitrile
4.1.2.27 0.03
-
 IC50 above 0.03 mM, at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl)-nicotinic acid
4.1.2.27 0.03
-
 IC50 above 0.03 mM, at pH 7.4 and 25°C Homo sapiens (R)-6-(4-(4-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)-nicotinonitrile
4.1.2.27 0.03
-
 IC50 above 0.03 mM, at pH 7.4 and 25°C Homo sapiens (S)-6-(4-(4-benzylphthalazin-1-yl)-2-(hydroxymethyl)piperazin-1-yl)nicotinonitrile
4.1.2.27 0.03
-
 IC50 above 0.03 mM, at pH 7.4 and 25°C Homo sapiens 6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile
4.1.2.27 0.03
-
 IC50 above 0.03 mM, at pH 7.4 and 25°C Homo sapiens 6-[4-(4-benzylphthalazin-1-yl)piperazin-1-yl]pyridine-3-carbonitrile