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Foretinib c-Met Inhibitor

Name: Foretinib
Brand: Selleck Chemicals
SKU: S1111
Rating: 5 (94 reviews)

Kat.-Nr.S1111

Foretinib ist ein ATP-kompetitiver Inhibitor von HGFR und VEGFR, hauptsächlich für Met (c-Met) und KDR mit IC50 von 0,4 nM und 0,9 nM in zellfreien Assays. Weniger wirksam gegen Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β und Tie-2, und geringe Aktivität gegenüber FGFR1 und EGFR. Phase 2.

Foretinib c-Met Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 632.65

Springe zu

Qualitätskontrolle

Charge: Reinheit: 99.94%

99.94

Verwandte Ziele	EGFR VEGFR PDGFR FGFR Src MEK CSF-1R FLT3 HER2 c-Kit
Weitere c-Met Inhibitoren	Tepotinib Dihexa SGX-523 PHA-665752 SU11274 BMS-777607 JNJ-38877605 Tivantinib PF-04217903 Savolitinib (AZD6094)

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Formulierung	Aktivitätsbeschreibung	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
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Chemische Informationen, Lagerung & Stabilität

Molekulargewicht	632.65	Formel	C₃₄H₃₄F₂N₄O₆	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	849217-64-7	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	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

Löslichkeit

In vitro
Charge:

DMSO : 100 mg/mL (158.06 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (158.06 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 127 mg/mL (200.74 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (158.06 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (158.06 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	30.000mg/ml (47.42mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

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 hemmt die Tyrosinkinasen der HGF-Rezeptorfamilie mit IC50-Werten von 0,4 nM für Met und 3 nM für Ron. XL880 hemmt auch KDR, Flt-1 und Flt-4 mit IC50-Werten von 0,9 nM, 6,8 nM bzw. 2,8 nM. XL880 hemmt das Koloniewachstum von B16F10-, A549- und HT29-Zellen mit IC50-Werten von 40 nM, 29 nM bzw. 165 nM. Eine aktuelle Studie zeigt, dass XL880 das Zellwachstum in Magenkarzinom-Zelllinien MKN-45 und KATO-III unterschiedlich beeinflusst. XL880 hemmt die Phosphorylierung von MET und nachgeschalteten Signalmolekülen in MKN-45-Zellen, während es GFGR2 in KATO-III-Zellen angreift.
Kinase-Assay	Kinase-Inhibitions-Assay
Kinase-Assay	Die Kinase-Inhibition wird unter Verwendung eines von drei Assay-Formaten untersucht: [³³P]Phosphoryltransfer, Luciferase-gekoppelte Chemilumineszenz oder AlphaScreen-Tyrosinkinase-Technologie. IC50-Werte werden durch nichtlineare Regressionsanalyse unter Verwendung von XLFit berechnet.³³P-Phosphoryltransfer-Kinase-Assay-Reaktionen werden in 384-Well-Mikrotiterplatten mit weißem, klarem Boden und hoher Bindung (Greiner, Monroe, NC) durchgeführt. Die Platten werden mit 2 μg/Well Protein oder Peptidsubstrat in einem Volumen von 50 μL Beschichtungspuffer beschichtet, der 40 μg/mL Substrat (Poly(Glu, Tyr) 4:1, 22,5 mM Na2CO₃, 27,5 mM NaHCO₃, 50 mM NaCl und 3 mM NaN₃) enthielt. Beschichtete Platten werden nach Inkubation über Nacht bei Raumtemperatur (RT) einmal mit 50 μL Assay-Puffer gewaschen. Testsubstanzen und Enzyme werden mit ³³P-γ-ATP (3,3 μCi/nmol) in einem Gesamtvolumen von 20 μL kombiniert. Die Reaktionsmischung wird 2 Stunden bei RT inkubiert und durch Aspiration beendet. Die Mikrotiterplatten werden anschließend 6 Mal mit 0,05% Tween-PBS-Puffer (PBST) gewaschen. Szintillationsflüssigkeit (50 μL/Well) wird hinzugefügt und das inkorporierte ³³P wird mittels Flüssigkeitsszintillationsspektrometrie unter Verwendung eines MicroBeta-Szintillationszählers gemessen.Luciferase-gekoppelte Chemilumineszenz-Assay-Reaktionen werden in 384-Well-Mikrotiterplatten mit weißer, mittlerer Bindung (Greiner) durchgeführt. In einem ersten Schritt werden Enzym und Verbindung kombiniert und 60 Minuten inkubiert; die Reaktionen werden durch Zugabe von ATP und Peptidsubstrat (Poly(Glu, Tyr) 4:1) in einem Endvolumen von 20 μL initiiert und 2-4 Stunden bei RT inkubiert. Nach der Kinase-Reaktion wird ein 20 μL Aliquot von Kinase Glo (Promega, Madison, WI) hinzugefügt und das Lumineszenzsignal wird mit einem Victor-Plattenleser gemessen. Der gesamte ATP-Verbrauch ist auf 50% begrenzt. AlphaScreenTM Tyrosinkinase-Assay-Donor-Beads, die mit Streptavidin beschichtet sind, und Akzeptor-Beads, die mit PY100 Anti-Phosphotyrosin-Antikörper beschichtet sind, werden verwendet. Biotinyliertes Poly(Glu,Tyr) 4:1 wird als Substrat verwendet. Die Substratphosphorylierung wird durch Zugabe von Donor-/Akzeptor-Beads durch Lumineszenz nach der Bildung des Donor-Akzeptor-Bead-Komplexes gemessen. Kinase und Testsubstanzen werden kombiniert und 60 Minuten vorinkubiert, gefolgt von der Zugabe von ATP und biotinyliertem Poly(Glu, Tyr) in einem Gesamtvolumen von 20 μL in 384-Well-Mikrotiterplatten mit weißer, mittlerer Bindung (Greiner). Die Reaktionsmischungen werden 1 Stunde bei Raumtemperatur inkubiert. Die Reaktionen werden durch Zugabe von 10 μL einer 15-30 μg/mL AlphaScreen-Bead-Suspension, enthaltend 75 mM Hepes, pH 7,4, 300 mM NaCl, 120 mM EDTA, 0,3% BSA und 0,03% Tween-20, abgebrochen. Nach 2-16 Stunden Inkubation bei Raumtemperatur werden die Platten mit einem AlphaQuest-Lesegerät ausgelesen.
In vivo	Eine einzelne orale Dosis von 100 mg/kg XL880 führt zu einer erheblichen Hemmung der Phosphorylierung von B16F10-Tumor-Met und der Liganden (z. B. HGF oder VEGF)-induzierten Rezeptorphosphorylierung von Met in der Leber und Flk-1/KDR in der Lunge, die beide über 24 Stunden anhielten. Die Behandlung mit XL880 (30-100 mg/kg, einmal täglich, orale Gavage) führt zu einer Reduktion der Tumorlast. Die Lungenoberflächentumorlast wurde nach Behandlung mit 30 bzw. 100 mg/kg XL880 um 50 % bzw. 58 % reduziert. Die XL880-Behandlung von Mäusen mit B16F10-Solidtumoren führte auch zu einer dosisabhängigen Tumorwachstumshemmung von 64 % und 87 % bei 30 bzw. 100 mg/kg. In beiden Studien war die Verabreichung von XL880 gut verträglich, ohne signifikanten Körpergewichtsverlust. XL880 wurde entwickelt, um die abnormale Signalübertragung von HGF durch Met und gleichzeitig mehrere an der Tumorangiogenese beteiligte Rezeptor-Tyrosinkinasen zu hemmen. XL880 verursachte innerhalb von 2 bis 4 Stunden Tumorblutungen und Nekrosen in menschlichen Xenotransplantaten, und maximale Tumornektrose wurde nach 96 Stunden (nach fünf täglichen Dosen) beobachtet, was zu einer vollständigen Regression führte.
Literatur	[1] http://www.ncbi.nlm.nih.gov/pubmed?term=19808973%20 [2] https://pubmed.ncbi.nlm.nih.gov/21655918/ [3] https://pubmed.ncbi.nlm.nih.gov/20472683/

Anwendungen

Methoden	Biomarker	Bilder	PMID
Western blot	pROS1 / tROS1 / pSHP2 / pERK / ERK p-MDM2 / p53 / PUMA p-Met / Met / p-Akt / Akt		24218589
Growth inhibition assay	Cell viability		29854314

Klinische Studieninformationen

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
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

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