1997
DOI: 10.1126/science.276.5314.955
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Structures of the Tyrosine Kinase Domain of Fibroblast Growth Factor Receptor in Complex with Inhibitors

Abstract: A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties tha… Show more

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Cited by 1,036 publications
(861 citation statements)
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“…SU5402 is a specific antagonist for FGFR1 and induces a conformational change in the nucleotide-binding loop of FGFR1. In mammalian in vitro assays, even at a high concentration of 50 µM, SU5402 does not block tyrosine phosphorylation of insulin and epidermal growth factor receptors and is only a weak inhibitor of phosphorylation of the plateletderived growth factor receptor (Mohammadi et al 1997). In the present study, treatment of ascidian embryos with SU5402 significantly inhibited ERK phosphorylation at 2 µM (Fig.…”
Section: Specificities Of Su5402 and U0126supporting
confidence: 47%
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“…SU5402 is a specific antagonist for FGFR1 and induces a conformational change in the nucleotide-binding loop of FGFR1. In mammalian in vitro assays, even at a high concentration of 50 µM, SU5402 does not block tyrosine phosphorylation of insulin and epidermal growth factor receptors and is only a weak inhibitor of phosphorylation of the plateletderived growth factor receptor (Mohammadi et al 1997). In the present study, treatment of ascidian embryos with SU5402 significantly inhibited ERK phosphorylation at 2 µM (Fig.…”
Section: Specificities Of Su5402 and U0126supporting
confidence: 47%
“…To inhibit the FGF signaling pathway, embryos were treated with 2 µM SU5402 (Calbiochem, San Diego, CA, USA) for 2 h, or 2 µM U0126 (Promega, Madison, WI, USA) for 20 min. SU5402 belongs to a new family of FGF signaling inhibitors that bind specifically to the active sites of FGFR kinase domains (Mohammadi et al 1997). U0126 is an MEK inhibitor that inhibits both the activation of MEK by Raf and the activation of ERK by MEK (Favata et al 1998).…”
Section: Treatment With Growth Factor and Inhibitorsmentioning
confidence: 99%
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“…Additional cell lines and their culture conditions have been described previously [26]. For functional analyses, cells were incubated in medium containing the FGFR1 inhibitor SU5402 (Calbiochem, Darmstadt, Germany) [27].…”
Section: Cell Linesmentioning
confidence: 99%
“…In this work, we first examined the early stages of the development of the epibranchial placodes in zebrafish embryos by using sox3 as a molecular marker. Next, we examined the requirement for FGF signaling in these processes using a fgf8-deficient mutant line (acerebellar; ace; Reifers et al, 1998) and a pharmacological inhibitor of the FGF receptor (Mohammadi et al, 1997;Leger and Brand, 2002;Maroon et al, 2002). This investigation revealed the essential role of the FGF signal in the initial specification of the epibranchial placode in zebrafish embryos.…”
Section: Introductionmentioning
confidence: 99%