Literature summary for 4.1.2.27 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 .

Cloned(Commentary)

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

Crystallization (Commentary)

Crystallization (Comment)	Organism
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

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O95470	-	-

Purification (Commentary)

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

Substrates and Products (Substrate)

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

Subunits

Subunits	Comment	Organism
homodimer	-	Homo sapiens

Synonyms

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

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
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
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
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
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
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
0.0017	-	at pH 7.4 and 25°C	Homo sapiens	(R)-6-(4-(4-benzylphthalazin-1-yl)-2-ethylpiperazin-1-yl)nicotinonitrile
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
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
0.0025	-	at pH 7.4 and 25°C	Homo sapiens	(R)-6-(4-(4-benzylphthalazin-1-yl)-2-isopropylpiperazin-1-yl)-nicotinonitrile
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
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
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
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
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
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
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
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
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
0.03	-	at pH 7.4 and 25°C	Homo sapiens	(R)-6-(2-methyl-4-(4-phenethylphthalazin-1-yl)piperazin-1-yl)nicotinonitrile