UniProt UniProt http://www.uniprot.org Orally Active 7-Substituted (4-Benzyl-phthalazin-1-yl)-2-methyl-piperazin-1-yl]-nicotinonitriles as Active-site Inhibitors of Sphingosine-1-Phosphate Lyase for the Treatment of Multiple Sclerosis. Orally Active 7-Substituted (4-Benzyl-phthalazin-1-yl)-2-methyl-piperazin-1-yl]-nicotinonitriles as Active-site Inhibitors of Sphingosine-1-Phosphate Lyase for the Treatment of Multiple Sclerosis. J. Med. Chem. (0022-2623) 2014 imex curation Weiler S., Braendlin N., Beerli C., Bergsdorf C., Schubart A., Srinivas H., Oberhauser B., Billich A. sven.weiler@novartis.com 21-Jul-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Weiler S., Braendlin N., Beerli C., Bergsdorf C., Schubart A., Srinivas H., Oberhauser B., Billich A. sven.weiler@novartis.com Accepted 2014-JUL-02 by MGT J. Med. Chem. (0022-2623) 2014 imex curation compound_31 (R)-6-(4-(4-Benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl)nicotinonitrile small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) sgpl1_human Sphingosine-1-phosphate lyase 1 Sphingosine-1-phosphate aldolase SGPL1 KIAA1252 protein protein human Homo sapiens Human MPSTDLLMLKAFEPYLEILEVYSTKAKNYVNGHCTKYEPWQLIAWSVVWTLLIVWGYEFVFQPESLWSRFKKKCFKLTRKMPIIGRKIQDKLNKTKDDISKNMSFLKVDKEYVKALPSQGLSSSAVLEKLKEYSSMDAFWQEGRASGTVYSGEEKLTELLVKAYGDFAWSNPLHPDIFPGLRKIEAEIVRIACSLFNGGPDSCGCVTSGGTESILMACKAYRDLAFEKGIKTPEIVAPQSAHAAFNKAASYFGMKIVRVPLTKMMEVDVRAMRRAISRNTAMLVCSTPQFPHGVIDPVPEVAKLAVKYKIPLHVDACLGGFLIVFMEKAGYPLEHPFDFRVKGVTSISADTHKYGYAPKGSSLVLYSDKKYRNYQFFVDTDWQGGIYASPTIAGSRPGGISAACWAALMHFGENGYVEATKQIIKTARFLKSELENIKGIFVFGNPQLSVIALGSRDFDIYRLSNLMTAKGWNLNQLQFPPSIHFCITLLHARKRVAIQFLKDIRESVTQIMKNPKAKTTGMGAIYGMAQTTVDRNMVAELSSVFLDSLYSTDTVTQGSQMNGSPKPH 3B16FDEFC4B2FDB6 compound-pyridoxal_5__phosphate-1 1 3 unspecified role unspecified role neutral component neutral component cytoplasmic_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain lys353 n6pydoxlys N6-pyridoxal phosphate-L-lysine (2S)-2-amino-6-[([3-hydroxy-2-methyl-5-phosphonooxymethylpyridin-4-yl]methylidene)amino]hexanoic acid MOD_RES N6-(pyridoxal phosphate)lysine N6-pyridoxal phosphate-L-lysine N6PydoxLys Pyridoxal phosphate Pyridoxal phosphate (Schiff Base formed to lysine) PyridoxalPhosphate certain certain sequence position certain certain certain sequence position certain spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection 2 inhibitor inhibitor neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Fig 4a/ Table 4 2.40 A R-factor: 0.179, R-free: 0.206