GNF-5837

GNF-5837

CAT N°: 14883
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From 85.00 72.25

Tropomyosin-related kinases (Trks) are receptor tyrosine kinases activated by peptides, including neurotrophins. They have prominent roles in the development of central and peripheral nervous systems, vascular cell survival, and cancer.{30894} Rearrangement of genes for Trks with the transcription factor Tel, producing Tel-Trk fusion proteins, are associated with various types of cancer.{30895,30893} GNF-5837 is a potent, bioavailable pan-Trk inhibitor that blocks the proliferation of cells expressing Tel-TrkA, Tel-TrkB, and Tel-TrkC (IC50s = 7, 9, and 11 nM, respectively).{30893} It less effectively inhibits c-Kit and PDGFR? (IC50s = 0.91 and 0.87 µM, respectively), while requiring micromolar concentrations to inhibit an array of other receptor and non-receptor tyrosine kinases. GNF-5837 inhibits the growth of Ba/F3 and rat intestinal epithelial (RIE) cells expressing both TrkA and nerve growth factor (NGF) with IC50 values of 42 and 17 nM, respectively, but does not have anti-proliferative activity of parental cells at concentrations up to 10 µM.{30893} GNF-5837 displays good bioavailability in mice and rats when given intravenously but not orally.{30893} It induces regression of tumor xenografts derived from RIE cells expressing both TrkA and NGF.{30893}

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