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The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.<\/jats:p>","DOI":"10.1126\/science.276.5314.955","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:45:15Z","timestamp":1027748715000},"page":"955-960","source":"Crossref","is-referenced-by-count":989,"title":["Structures of the Tyrosine Kinase Domain of Fibroblast Growth Factor Receptor in Complex with Inhibitors"],"prefix":"10.1126","volume":"276","author":[{"given":"Moosa","family":"Mohammadi","sequence":"first","affiliation":[{"name":"M. Mohammadi, B. K. Yeh, J. Schlessinger, Department of Pharmacology, New York University Medical Center, New York, NY 10016, USA."},{"name":"G. McMahon, L. Sun, C. Tang, P. Hirth, SUGEN, Redwood City, CA 94063, USA."},{"name":"S. R. 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Preparation of 3-[(3-(2-carboxyethyl)-4-methylpyrrol-2-yl)methylene]-2-indolinone (SU5402) was as follows: A reaction mixture of 134.0 mg (1.0 mmol) of oxindole 217.43 mg (1.2 mmol) of 3-(2-carboxyethyl)-4-methylpyrrol-2-carboxaldehyde and three drops of piperidine in 3 ml of ethanol was stirred at 90\u00b0C for 3 hours. After cooling the precipitate was filtered washed with cold ethanol and dried to yield 172.4 mg (58%) of SU5402 as a yellow solid. NMR spectroscopy showed that SU5402 exists predominantly in the cis configuration."},{"key":"e_1_3_1_19_2","unstructured":"The compounds were dissolved in dimethylsulfoxide (DMSO) as 100 mM stock solutions and stored at 4\u00b0C. The compounds were then diluted in DMSO to a concentration 20\u00d7 the final concentration used in the in vitro kinase reactions. 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