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Products are for research use only. Not for human use. We do not sell to patients.
(XL880; GSK1363089; GSK089; EXEL-2880)
Foretinib Chemical Structure
|Product name: Foretinib|
|Cat. No.: HY-10338|
Foretinib (GSK1363089; XL880; EXEL-2880; GSK089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR.
IC50 value: 0.4 nM/0.9 nM (Met/KDR) 
in vitro: XL880 inhibits HGF receptor family tyrosine kinases with IC50 values of 0.4 nM for Met and 3 nM for Ron. XL880 also inhibits KDR, Flt-1, and Flt-4 with IC50 values of 0.9 nM, 6.8 nM and 2.8 nM, respectively. XL880 inhibits colony growth of B16F10, A549 and HT29 cells with IC50 of 40 nM, 29 nM and 165 nM, respectively . A recent study indicates XL880 affects cell growth differently in gastric cancer cell lines MKN-45 and KATO-III. XL880 inhibits phosphorylation of MET and downstream signaling molecules in MKN-45 cells, while targets GFGR2 in KATO-III cells .
in vivo: A single 100 mg/kg oral gavage dose of XL880 results in substantial inhibition of phosphorylation of B16F10 tumor Met and ligand (e.g., HGFor VEGF)-induced receptor phosphorylation of Met in liver and Flk-1/KDR in lung, which both persisted through 24 hours. Treatment with XL880 (30-100 mg/kg, once daily, oral gavage) results in reduction in tumor burden. The lung surface tumor burden is reduced by 50% and 58% following treatment with 30 and 100 mg/kg XL880, respectively. XL880 treatment of mice bearing B16F10 solid tumors also results in dose-dependent tumor growth inhibition of 64% and 87% at 30 and 100 mg/kg, respectively. For both studies, administration of XL880 is well tolerated with no significant body weight loss . XL880 is developed to target abnormal signaling of HGF through Met and simultaneously target several receptors tyrosine kinase involved in tumor angiogenesis. XL880 caused tumor hemorrhage and necrosis in human xenografts within 2 to 4 hours, and maximal tumornecrosis is observed at 96 hours (after five daily doses), resulting in complete regression .
|M.Wt||632.65||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO ≥122mg/mL Water <1.2mg/mL Ethanol ≥10mg/mL
|1 mg||5 mg||10 mg|
|1 mM||1.5807 mL||7.9033 mL||15.8065 mL|
|5 mM||0.3161 mL||1.5807 mL||3.1613 mL|
|10 mM||0.1581 mL||0.7903 mL||1.5807 mL|
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|Foretinib||NCIC Clinical Trials Group||Metastatic breast cancer||30-JUN-10||30-APR-13||Phase 2||13-AUG-13|
|GlaxoSmithKline plc||Renal cell carcinoma||30-JUN-06||31-JUL-12||Phase 2||08-NOV-13|
|NCIC Clinical Trials Group||Metastatic breast cancer||31-MAY-10||31-JAN-16||Phase 2||12-AUG-13|
|GlaxoSmithKline plc||Head and neck tumor||31-AUG-07||31-MAY-09||Phase 2||22-MAR-13|
|GlaxoSmithKline plc||Squamous cell carcinoma||31-AUG-07||31-MAY-09||Phase 2||22-MAR-13|
. Qian F, et al. Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Res, 2009, 69(20), 8009-8016.
. Kataoka Y, et al. Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks. Invest New Drugs, 2011.
2,4-Pyrimidinediamine with linker is a patent compound in WO2013055780A1, Page 71; multikinase inhibitor and has a -NH2 terminal linker for further synthesis.
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AMG-337 is a potent and highly selective small molecule ATP-competitive MET kinase inhibitor. AMG 337 inhibits MET kinase activity with an IC50 of < 5nM in enzymatic assays.
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AZD2932 is a new series of quinazoline ether inhibitor which potently inhibits VEGFR-2 and PDGFR with IC50s of 4 nM/8 nM/ 7 nM for PDGFR(beta)/VEGFR-2/Flt-3.
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