Home Protein Tyrosine Kinase c-Met Hämmare Foretinib (GSK1363089, XL880)

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Foretinib (GSK1363089, XL880) Tyrosinkinashämmare med flera mål

Kat.nr.: S1111

Foretinib är en ATP-kompetitiv hämmare av HGFR och VEGFR, främst för Met (c-Met) och KDR med IC50 på 0,4 nM och 0,9 nM i cellfria analyser. Mindre potent mot Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β och Tie-2, och liten aktivitet mot FGFR1 och EGFR. Fas 2.
Foretinib (GSK1363089, XL880) c-Met Hämmare Chemical Structure

Kemisk struktur

Molekylvikt: 632.65

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.94%
99.94

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer Analystyp Koncentration Inkubationstid Formulering Aktivitetsbeskrivning PMID
Daoy  Function Assay 0.5/1/2.5 μM 24 h DMSO inhibits the HGF-induced cMET pathway activation 25391241
ONS76 Function Assay 0.5/1/2.5 μM 24 h DMSO inhibits the HGF-induced cMET pathway activation 25391241
Daoy  Function Assay 0.5/1/2.5 μM 24 h DMSO inhibits HGF-mediated migration and invasion 25391241
ONS76 Function Assay 0.5/1/2.5 μM 24 h DMSO inhibits HGF-mediated migration and invasion 25391241
Daoy  Apoptosis Assay 1 μM 24 h DMSO induces apoptosis 25391241
Daoy  Growth Inhibition Assay 0.5/1/2.5 μM 24-96 h DMSO inhibits cell growth in a dose dependent manner 25391241
U251 Function Assay 100/300/900 nM 1 h DMSO inhibits the phosphorylation of MerTK  24658326
A172 Function Assay 100/300/900 nM 1 h DMSO inhibits the phosphorylation of MerTK  24658326
SF188 Function Assay 100/300/900 nM 1 h DMSO inhibits the phosphorylation of MerTK  24658326
U251 Function Assay 100/300/900 nM 1 h DMSO inhibits the activity of Axl, Tyro3 24658326
A172 Function Assay 100/300/900 nM 1 h DMSO inhibits the activity of Axl, Tyro3 24658326
SF188 Function Assay 100/300/900 nM 1 h DMSO inhibits the activity of Axl, Tyro3 24658326
U251 Function Assay 100/300/900 nM 1 h DMSO decreases Akt phosphorylation in a concentration dependent manner 24658326
A172 Function Assay 100/300/900 nM 1 h DMSO decreases Akt phosphorylation in a concentration dependent manner 24658326
SF188 Function Assay 100/300/900 nM 1 h DMSO decreases Akt phosphorylation in a concentration dependent manner 24658326
U251 Function Assay 100/300/900 nM 28 h DMSO induces PARP cleavage 24658326
SF188 Function Assay 100/300/900 nM 28 h DMSO induces PARP cleavage 24658326
SF188 Growth Inhibition Assay 100/300/900 nM 48 h DMSO reduces cell survival at 900 nM significantly 24658326
U251 Growth Inhibition Assay 100/300/900 nM 48 h DMSO reduces cell survival at 900 nM significantly 24658326
A172 Growth Inhibition Assay 100/300/900 nM 48 h DMSO reduces cell survival at 900 nM significantly 24658326
SF188 Function Assay 100/300/900 nM 24 h DMSO abrogates migration and invasion of glioma cells in a dose dependent manner 24658326
U251 Function Assay 100/300/900 nM 24 h DMSO abrogates migration and invasion of glioma cells in a dose dependent manner 24658326
A172 Function Assay 100/300/900 nM 24 h DMSO abrogates migration and invasion of glioma cells in a dose dependent manner 24658326
Ba/F3 Cell Viability Assay 0.0001-10 μM 72 h inhibits cell growth in a dose dependent manner 24218589
HCC78 Cell Viability Assay 0.01-10 μM 72 h inhibits cell growth in a dose dependent manner 24218589
SK-HEP1 Cell Viability Assay 0.25-1.5 μM 24 h inhibits cell growth in a dose dependent manner 22187171
SK-HEP2 Function Assay 1 μM 24 h blocks HGF-induced cell motility 22187171
SK-HEP2 Function Assay 1 μM 24 h causes G2/M phase arrest with reduction in the G0/G1 and S phases 22187171
MKN-45  Growth Inhibition Assay 0.01-10 μM 5 d IC50=8 nM 21655918
KATO-III Growth Inhibition Assay 0.01-10 μM 5 d IC50=30 nM 21655918
MKN-45  Function Assay 1 μM 24 h inhibits phosphorylation of MET, Akt, and ERK1/2 in MKN-45 21655918
KATO-III Function Assay 1 μM 24 h inhibits phosphorylation of MET, Akt, and ERK1/2 in MKN-45 21655918
H1648 Growth Inhibition Assay IC50=1.28 ±0.12 μM 21252284
H1573 Growth Inhibition Assay IC50=1.62 ± 0.05 μM 21252284
H596 Growth Inhibition Assay IC50=1.21 ± 0.17 μM 21252284
HOP92 Growth Inhibition Assay IC50=0.81 ± 0.29 μM 21252284
H69 Growth Inhibition Assay IC50=1.18 ± 0.08 μM 21252284
H1975 Growth Inhibition Assay IC50=1.39 ± 0.33 μM 21252284
SCC15 Growth Inhibition Assay IC50=0.63 ± 0.04 μM 21252284
HN5 Growth Inhibition Assay IC50=0.65 ± 0.26 μM 21252284
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met-dependent human MKN45 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.03 μM. 23628470
A549 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met-dependent human A549 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.08 μM. 23628470
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met-dependent human HT-29 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.15 μM. 23628470
H460 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met-independent human H460 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.18 μM. 23628470
SMMC7721 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met-dependent human SMMC7721 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.44 μM. 23628470
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against c-Met-dependent human U87MG cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 0.9 μM. 23628470
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.031 μM. 23644189
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.12 μM. 23644189
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.18 μM. 23644189
SMMC7721 Cytotoxicity assay 72 hrs Cytotoxicity against human SMMC7721 cells after 72 hrs by MTT assay, IC50 = 0.3 μM. 23644189
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 1.04 μM. 23644189
MKN45 Cytotoxicity assay Cytotoxicity against human MKN45 cells, IC50 = 0.008 μM. 23838381
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.023 μM. 23838381
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by DAPI staining-based fluorescence assay, IC50 = 0.029 μM. 23838381
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by DAPI staining-based fluorescence assay, IC50 = 0.165 μM. 23838381
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.17 μM. 23838381
NCI-H460 Cytotoxicity assay 72 hrs Cytotoxicity against human NCI-H460 cells after 72 hrs by MTT assay, IC50 = 0.21 μM. 23838381
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.26 μM. 23838381
SMMC7721 Cytotoxicity assay 72 hrs Cytotoxicity against human SMMC7721 cells after 72 hrs by MTT assay, IC50 = 0.32 μM. 23838381
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 0.47 μM. 23838381
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.032 μM. 24012712
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.11 μM. 24012712
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.19 μM. 24012712
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.21 μM. 24012712
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 1.08 μM. 24012712
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.032 μM. 24485123
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.13 μM. 24485123
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.16 μM. 24485123
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.19 μM. 24485123
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 1.1 μM. 24485123
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.032 μM. 24882675
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.19 μM. 24882675
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.21 μM. 24882675
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50 = 0.54 μM. 24882675
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.032 μM. 24996144
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.11 μM. 24996144
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.19 μM. 24996144
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.21 μM. 24996144
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 1.08 μM. 24996144
MKN45 Antiproliferative assay 72 hrs Antiproliferative activity against human MKN45 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.032 μM. 25282672
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.12 μM. 25282672
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.19 μM. 25282672
H460 Antiproliferative assay 72 hrs Antiproliferative activity against human H460 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 0.21 μM. 25282672
U87MG Antiproliferative assay 72 hrs Antiproliferative activity against human U87MG cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50 = 1.02 μM. 25282672
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.032 μM. 25438768
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.13 μM. 25438768
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.16 μM. 25438768
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.19 μM. 25438768
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 0.92 μM. 25438768
BA/F3 Function assay Inhibition of ROS1 (unknown origin) expressed in mouse BA/F3 cells, IC50 = 0.01 μM. 25461320
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.032 μM. 26169763
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.12 μM. 26169763
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.19 μM. 26169763
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.21 μM. 26169763
BT474 Function assay Inhibition of AXL in lapatinib-sensitive human BT474 cells, IC50 = 0.1 μM. 26555154
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells after 72 hrs by MTT assay, IC50 = 0.39 μM. 26810712
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.64 μM. 26810712
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 9.47 μM. 26810712
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.023 μM. 26897090
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.17 μM. 26897090
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.26 μM. 26897090
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as reduction in cell growth after 72 hrs by MTT assay, IC50 = 0.26 μM. 26923692
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as reduction in cell growth after 72 hrs by MTT assay, IC50 = 0.49 μM. 26923692
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells assessed as reduction in cell growth after 72 hrs by MTT assay, IC50 = 0.89 μM. 26923692
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as reduction in cell growth after 72 hrs by MTT assay, IC50 = 6.25 μM. 26923692
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.032 μM. 26944614
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.13 μM. 26944614
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.16 μM. 26944614
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.19 μM. 26944614
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 1.1 μM. 26944614
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells after 72 hrs by MTT assay, IC50 = 0.39 μM. 26964675
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.64 μM. 26964675
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 9.47 μM. 26964675
BA/F3 Antiproliferative assay 72 hrs Antiproliferative activity against mouse BA/F3 cells expressing TPR-Met after 72 hrs by CCK8 assay, IC50 = 0.0092 μM. 27068889
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells measured after 72 hrs by MTT assay, IC50 = 0.032 μM. 27155466
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells measured after 72 hrs by MTT assay, IC50 = 0.11 μM. 27155466
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells measured after 72 hrs by MTT assay, IC50 = 0.19 μM. 27155466
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells measured after 72 hrs by MTT assay, IC50 = 0.21 μM. 27155466
MKN45 Cytotoxicity assay Cytotoxicity against human MKN45 cells, IC50 = 0.008 μM. 27187857
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.023 μM. 27187857
HT-29 Cytotoxicity assay Cytotoxicity against human HT-29 cells, IC50 = 0.029 μM. 27187857
A549 Cytotoxicity assay Cytotoxicity against human A549 cells, IC50 = 0.165 μM. 27187857
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.17 μM. 27187857
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.26 μM. 27187857
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50 = 0.54 μM. 27187857
Sf9 Function assay 60 mins Inhibition of NH2-terminal His-tagged MET kinase domain (1051 to 1348 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells preincubated for 60 mins followed by (poly(Glu, Tyr) 4:1) substrate addition for 2 to 4 hrs by luciferase-c, IC50 = 0.0004 μM. 27299736
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met over-expressed human MKN45 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.032 μM. 27490023
A549 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met over-expressed human A549 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.14 μM. 27490023
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met over-expressed human HT-29 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.19 μM. 27490023
H460 Cytotoxicity assay 72 hrs Cytotoxicity against c-Met over-expressed human H460 cells assessed as cell growth inhibition after 72 hrs by MTT assay, IC50 = 0.21 μM. 27490023
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.15 μM. 28011202
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.25 μM. 28011202
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.32 μM. 28011202
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.25 μM. 28384549
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.29 μM. 28384549
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.36 μM. 28384549
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 0.96 μM. 28384549
MKN45 Antiproliferative assay 72 hrs Antiproliferative activity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.03 μM. 28716639
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.15 μM. 28716639
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.21 μM. 28716639
H460 Antiproliferative assay 72 hrs Antiproliferative activity against human H460 cells after 72 hrs by MTT assay, IC50 = 0.22 μM. 28716639
U87MG Antiproliferative assay 72 hrs Antiproliferative activity against human U87MG cells after 72 hrs by MTT assay, IC50 = 0.96 μM. 28716639
HCC827 Function assay Displacement of [3H]-cyclopamine from SMO V404M mutant in gefitinib resistant human HCC827 cells by scintillation counting, Ki = 0.0668 μM. 28787156
HCC827 Antiproliferative assay 72 hrs Antiproliferative activity against gefitinib resistant EGFR-mutated human HCC827 cells after 72 hrs by MTT assay, IC50 = 0.5 μM. 28787156
HCC827 Antitumor assay 15 mg/kg Antitumor activity against gefitinib resistant human HCC827 cells xenografted in balb/c athymic nu/nu mouse assessed as decrease in tumor size at 15 mg/kg/day, po 28787156
HCC827 Apoptosis assay 0.01 to 1 uM 72 hrs Induction of apoptosis in gefitinib resistant human HCC827 cells at 0.01 to 1 uM after 72 hrs by annexin V-FITC-propidium iodide staining-based flow cytometry method relative to control 28787156
HCC827 Function assay 0.1 to 0.5 uM 72 hrs Inhibition of MET phosphorylation at Tyr1234/1235 in gefitinib resistant human HCC827 cells at 0.1 to 0.5 uM after 72 hrs by Western blotting method 28787156
HCC827 Function assay 0.1 to 0.5 uM 72 hrs Downregulation of SMO expression in gefitinib resistant human HCC827 cells at 0.1 to 0.5 uM after 72 hrs by Western blotting method 28787156
HCC827 Function assay 0.1 to 0.5 uM 72 hrs Inhibition of MET in gefitinib resistant human HCC827 cells assessed as decrease in MAPK44/42 phosphorylation at Thr202/Tyr204 at 0.1 to 0.5 uM after 72 hrs by Western blotting method 28787156
HCC827 Function assay 0.1 to 0.5 uM 72 hrs Inhibition of MET in gefitinib resistant human HCC827 cells assessed as decrease in AKT phosphorylation at Ser473 at 0.1 to 0.5 uM after 72 hrs by Western blotting method 28787156
HCC827 Function assay 0.1 to 0.5 uM 72 hrs Inhibition of MET/SMO V404M mutant in gefitinib resistant human HCC827 cells assessed as decrease in vimentin expression at 0.1 to 0.5 uM after 72 hrs by Western blotting method 28787156
HCC827 Antitumor assay 20 mg/kg Antitumor activity against gefitinib resistant human HCC827 cells xenografted in balb/c athymic nu/nu mouse assessed as decrease in tumor size at 20 mg/kg/day, po 28787156
HCC827 Antitumor assay 20 mg/kg Antitumor activity against gefitinib resistant human HCC827 cells xenografted in balb/c athymic nu/nu mouse assessed as decrease in tumor size at 20 mg/kg/day, po in presence of gefitinib 28787156
HCC827 Antitumor assay 20 mg/kg Antitumor activity against gefitinib resistant human HCC827 cells xenografted in balb/c athymic nu/nu mouse assessed as decrease in tumor size at 20 mg/kg/day, po in presence of osimertinib 28787156
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 1.48 μM. 29107421
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 1.74 μM. 29107421
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 2.88 μM. 29107421
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 3.92 μM. 29107421
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.26 μM. 29197731
NCI-H460 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H460 cells after 72 hrs by MTT assay, IC50 = 0.28 μM. 29197731
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.32 μM. 29197731
U87MG Antiproliferative assay 72 hrs Antiproliferative activity against human U87MG cells after 72 hrs by MTT assay, IC50 = 0.91 μM. 29197731
HepG2 Cytotoxicity assay 72 hrs Cytotoxicity against human HepG2 cells after 72 hrs by MTT assay, IC50 = 2.27 μM. 29203143
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 2.76 μM. 29203143
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 3.13 μM. 29203143
PC3 Antiproliferative assay 72 hrs Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay, IC50 = 0.39 μM. 29331754
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.64 μM. 29331754
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 9.47 μM. 29331754
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
fibroblast cells qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
fibroblast cells qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.32 μM. 30216852
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay, IC50 = 0.48 μM. 30216852
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 0.76 μM. 30216852
MKN45 Antiproliferative assay 72 hrs Antiproliferative activity against human MKN45 cells after 72 hrs by MTT assay, IC50 = 0.0023 μM. 30248654
EBC1 Antiproliferative assay 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs by MTT assay, IC50 = 0.0048 μM. 30248654
SNU5 Antiproliferative assay 72 hrs Antiproliferative activity against human SNU5 cells after 72 hrs by MTT assay, IC50 = 0.0089 μM. 30248654
BAF3 Function assay 72 hrs Inhibition of TPR-tagged met (unknown origin) expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50 = 0.0092 μM. 30248654
NCI-H460 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H460 cells after 72 hrs by MTT assay, IC50 = 0.0396 μM. 30248654
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity in human MKN45 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 0.041 μM. 31079967
NCI-H460 Cytotoxicity assay 72 hrs Cytotoxicity in human NCI-H460 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 0.18 μM. 31079967
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity in human HT-29 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 0.22 μM. 31079967
MDA-MB-231 Cytotoxicity assay 72 hrs Cytotoxicity in human MDA-MB-231 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 0.52 μM. 31079967
sf21 Function assay 60 mins Inhibition of wild type N-terminal NH-tagged and avi-tagged dephosphorylated c-MET (956 to 1390 residues) (unknown origin) expressed in sf21 cells using poly (Glu,Tyr) as substrate measured after 60 mins by ADP-Glo kinase assay, IC50 = 0.002512 μM. 31531204
sf21 Function assay 60 mins Inhibition of N-terminal NH-tagged and avi-tagged dephosphorylated c-MET D1228V mutant (956 to 1390 residues) (unknown origin) expressed in sf21 cells using poly (Glu,Tyr) as substrate measured after 60 mins by ADP-Glo kinase assay, IC50 = 0.002512 μM. 31531204
NCI-H1993 Growth inhibition assay 3 days Growth inhibition of CRISPR/Cas9 modified human NCI-H1993 cells harboring cMET D1228V mutant incubated for 3 days by cell titer-glo luminescent cell viability assay, GI50 = 0.05248 μM. 31531204
NCI-H1993 Growth inhibition assay 3 days Growth inhibition of wild type human NCI-H1993 cells incubated for 3 days by cell titer-glo luminescent cell viability assay, GI50 = 0.06166 μM. 31531204
NCI-H1993 Function assay 4 hrs Inhibition of c-Met phosphorylation at Tyr 1234/Tyr1235 residues in human NCI-H1993 cells incubated for 4 hrs by HTRF assay, IC50 = 0.2138 μM. 31531204
NCI-H1993 Function assay 4 hrs Inhibition of c-MET D1228V mutant phosphorylation at Tyr1234/Tyr1235 residues in CRISPR/Cas9 modified human NCI-H1993 cells incubated for 4 hrs by HTRF assay, IC50 = 0.2138 μM. 31531204
NCI-H1993 Function assay 1 uM 4 hrs Inhibition of c-MET D1228V mutant in CRISPR/Cas9 modified human NCI-H1993 cells assessed as reduction in AKT phosphorylation at 1 uM after 4 hrs by Western blot analysis 31531204
NCI-H1993 Function assay 1 uM 4 hrs Inhibition of c-Met phosphorylation in human NCI-H1993 cells at 1 uM after 4 hrs by Western blot analysis 31531204
NCI-1993 Function assay 1 uM 4 hrs Inhibition of c-MET in human NCI-1993 cells assessed as reduction in AKT phosphorylation at 1 uM after 4 hrs by Western blot analysis 31531204
NCI-H1993 Function assay 1 uM 4 hrs Inhibition of c-Met D1228V mutant phosphorylation in CRISPR/Cas9 modified human NCI-H1993 cells at 1 uM after 4 hrs by Western blot analysis 31531204
sf21 Function assay Binding affinity to wild type N-terminal NH-tagged and avi-tagged dephosphorylated c-MET (956 to 1390 residues) (unknown origin) expressed in sf21 cells by SPR analysis 31531204
sf21 Function assay Binding affinity to N-terminal NH-tagged and avi-tagged dephosphorylated c-MET D1228V mutant (956 to 1390 residues) (unknown origin) expressed in sf21 cells by SPR analysis 31531204
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 2.4 μM. 31546197
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 2.4 μM. 31546197
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells assessed as reduction in cell viability after 72 hrs by MTT assay, IC50 = 2.4 μM. 31546197
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 0.2 μM. 31629631
H460 Cytotoxicity assay 72 hrs Cytotoxicity against human H460 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 1.14 μM. 31629631
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 1.49 μM. 31629631
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 1.76 μM. 31629631
U87MG Cytotoxicity assay 72 hrs Cytotoxicity against human U87MG cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay, IC50 = 2.17 μM. 31629631
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt 632.65 Formel

C34H34F2N4O6

 Lagring (från mottagningsdatumet)
CAS-nr 849217-64-7 Ladda ner SDF Lagring av stamlösningar

Synonymer GSK1363089, EXEL-2880, XL-880, GSK089 Smiles COC1=CC2=C(C=CN=C2C=C1OCCCN3CCOCC3)OC4=C(C=C(C=C4)NC(=O)C5(CC5)C(=O)NC6=CC=C(C=C6)F)F

Löslighet (Solubility)

In vitro
Batch:

DMSO : 100 mg/mL (158.06 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa Koncentration Volym Molekylvikt
Utspädningsräknare Molekylviktsräknare

In vivo
Batch:

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

mg/kg g μL

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH2O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC50/Ki
Met
(Cell-free assay)
0.4 nM
KDR
(Cell-free assay)
0.86 nM
Tie-2
(Cell-free assay)
1.1 nM
VEGFR3/FLT4
(Cell-free assay)
2.8 nM
RON
(Cell-free assay)
3 nM
FLT3
(Cell-free assay)
3.6 nM
PDGFRα
(Cell-free assay)
3.6 nM
Kit
(Cell-free assay)
6.7 nM
VEGFR1/FLT1
(Cell-free assay)
6.8 nM
PDGFRβ
(Cell-free assay)
9.6 nM
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.
Kinasanalys
Kinashämmande analys
Kinashämning undersöks med hjälp av ett av tre analysformat: [33P]fosforylöverföring, luciferaskopplad kemiluminiscens eller AlphaScreen tyrosinkinas-teknik. IC50 beräknas genom icke-linjär regressionsanalys med XLFit.33P-fosforylöverföringskinasanalys Reaktioner utförs i 384-brunns vita, genomskinliga botten, högbindande mikrotiterplattor (Greiner, Monroe, NC). Plattorna beläggs med 2 μg/brunn protein eller peptidsubstrat i en volym på 50 μL beläggningsbuffert innehållande 40 μg/mL substrat (poly(Glu, Tyr) 4:1, 22,5 mM Na2CO3, 27,5 mM NaHCO3, 50 mM NaCl och 3 mM NaN3). Belagda plattor tvättas en gång med 50 μL analysbuffert efter inkubation över natten vid rumstemperatur (RT). Testföreningar och enzymer kombineras med 33P-γ-ATP (3,3 μCi/nmol) i en total volym på 20 μL. Reaktionsblandningen inkuberas vid RT i 2 timmar och avbryts genom aspiration. Mikrotiterplattorna tvättas därefter 6 gånger med 0,05% Tween-PBS-buffert (PBST). Scintillationsvätska (50 μL/brunn) tillsätts och inkorporerad 33P mäts med vätskescintillationsspektrometri med hjälp av en MicroBeta-scintillationsräknare.Luciferaskopplad kemiluminiscensanalys Reaktioner utförs i 384-brunns vita, medelbindande mikrotiterplattor (Greiner). I ett första steg kombineras enzym och förening och inkuberas i 60 minuter; reaktioner initieras genom tillsats av ATP och peptidsubstrat (poly(Glu, Tyr) 4:1) i en slutvolym på 20 μL, och inkuberas vid RT i 2-4 timmar. Efter kinasreaktionen tillsätts en 20 μL alikvot av Kinase Glo (Promega, Madison, WI) och luminiscenssignalen mäts med en Victor-plattläsare. Total ATP-konsumtion begränsas till 50%. AlphaScreenTM Tyrosinkinasanalys Donor-kulor belagda med streptavidin och acceptor-kulor belagda med PY100 anti-fosfotyrosin-antikropp används. Biotinylerat poly(Glu,Tyr) 4:1 används som substrat. Substratfosforylering mäts genom tillsats av donor-/acceptor-kulor genom luminiscens efter bildandet av donor-acceptor-kulkomplex. Kinas och testföreningar kombineras och förinkuberas i 60 minuter, följt av tillsats av ATP och biotinylerat poly(Glu, Tyr) i en total volym på 20 μL i 384-brunns vita, medelbindande mikrotiterplattor (Greiner). Reaktionsblandningarna inkuberas i 1 timme vid rumstemperatur. Reaktioner släcks genom tillsats av 10 μL av 15-30 μg/mL AlphaScreen-kulssuspension innehållande 75 mM Hepes, pH 7,4, 300 mM NaCl, 120 mM EDTA, 0,3% BSA och 0,03% Tween-20. Efter 2-16 timmars inkubation vid rumstemperatur läses plattorna av med en AlphaQuest-läsare.
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.
Referenser

Applikationer (Applications)

Metoder Biomarkörer Bilder PMID
Western blot pROS1 / tROS1 / pSHP2 / pERK / ERK p-MDM2 / p53 / PUMA p-Met / Met / p-Akt / Akt
S1111-WB3
24218589
Growth inhibition assay Cell viability
S1111-viability1
29854314

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer Rekrytering Tillstånd Sponsor/Samarbetspartners Startdatum Faser
NCT00920192 Completed
Carcinoma Hepatocellular
GlaxoSmithKline
 August 12 2009 Phase 1
NCT00742261 Completed
Solid Tumours
GlaxoSmithKline
 August 11 2008 Phase 1
NCT00725764 Completed
Neoplasms Head and Neck
GlaxoSmithKline
 August 27 2007 Phase 2
NCT00725712 Completed
Neoplasms Gastrointestinal Tract
GlaxoSmithKline
 March 31 2007 Phase 2
NCT00743067 Completed
Solid Tumours
GlaxoSmithKline
 August 9 2006 Phase 1