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Foretinib c-Met inibitore

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

N. Cat.S1111

Foretinib è un inibitore ATP-competitivo di HGFR e VEGFR, principalmente per Met (c-Met) e KDR con IC50 di 0,4 nM e 0,9 nM in saggi acellulari. Meno potente contro Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β e Tie-2, e scarsa attività verso FGFR1 e EGFR. Fase 2.

Foretinib c-Met inibitore Chemical Structure

Struttura chimica

Peso molecolare: 632.65

Vai a

Controllo Qualità

Lotto: Purezza: 99.94%

99.94

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

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dellattività	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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Informazioni chimiche, conservazione e stabilità

Peso molecolare	632.65	Formula	C₃₄H₃₄F₂N₄O₆	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	849217-64-7	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	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

Solubilità

In vitro
Lotto:

DMSO : 100 mg/mL (158.06 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

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 inibisce le Protein Tyrosine Kinases della famiglia dei recettori HGF con valori di IC50 di 0,4 nM per Met e 3 nM per Ron. XL880 inibisce anche KDR, Flt-1 e Flt-4 con valori di IC50 rispettivamente di 0,9 nM, 6,8 nM e 2,8 nM. XL880 inibisce la crescita delle colonie di cellule B16F10, A549 e HT29 con IC50 rispettivamente di 40 nM, 29 nM e 165 nM. Uno studio recente indica che XL880 influenza la crescita cellulare in modo diverso nelle linee cellulari di cancro gastrico MKN-45 e KATO-III. XL880 inibisce la fosforilazione di MET e delle molecole di segnalazione a valle nelle cellule MKN-45, mentre bersaglia GFGR2 nelle cellule KATO-III.
Saggio chinasico	Saggio di Inibizione Chinasica
Saggio chinasico	L'inibizione chinasica viene investigata utilizzando uno dei tre formati di saggio: trasferimento di [³³P]fosforile, chemioluminescenza accoppiata a luciferasi o tecnologia AlphaScreen Protein Tyrosine Kinase. Gli IC50 sono calcolati mediante analisi di regressione non lineare utilizzando XLFit. Saggio chinasico con trasferimento di ³³P-fosforile Le reazioni vengono eseguite in piastre per microtitolazione bianche a 384 pozzetti, con fondo trasparente e ad alto legame (Greiner, Monroe, NC). Le piastre sono rivestite con 2 μg/pozzetto di proteina o substrato peptidico in un volume di 50 μL di tampone di rivestimento contenente 40 μg/mL di substrato (poli(Glu, Tyr) 4:1, 22,5 mM Na2CO₃, 27,5 mM NaHCO₃, 50 mM NaCl e 3 mM NaN₃. Le piastre rivestite vengono lavate una volta con 50 μL di tampone di saggio dopo un'incubazione notturna a temperatura ambiente (TA). I composti di prova e gli enzimi sono combinati con ³³P-γ-ATP (3,3 μCi/nmol) in un volume totale di 20 μL. La miscela di reazione viene incubata a TA per 2 ore e terminata per aspirazione. Le piastre per microtitolazione vengono successivamente lavate 6 volte con tampone Tween-PBS (PBST) allo 0,05%. Viene aggiunto liquido di scintillazione (50 μL/pozzetto) e il ³³P incorporato viene misurato mediante spettrometria a scintillazione liquida utilizzando un contatore a scintillazione MicroBeta. Saggio di chemioluminescenza accoppiata a luciferasi Le reazioni vengono condotte in piastre per microtitolazione bianche a 384 pozzetti con legame medio (Greiner). In una prima fase, enzima e composto vengono combinati e incubati per 60 minuti; le reazioni vengono avviate mediante l'aggiunta di ATP e substrato peptidico (poli(Glu, Tyr) 4:1) in un volume finale di 20 μL, e incubate a TA per 2-4 ore. Dopo la reazione chinasica, viene aggiunta un'aliquota di 20 μL di Kinase Glo (Promega, Madison, WI) e il segnale di luminescenza viene misurato utilizzando un lettore di piastre Victor. Il consumo totale di ATP è limitato al 50%. Saggio di Protein Tyrosine Kinase AlphaScreen™ Vengono utilizzate perle donatrici rivestite con streptavidina e perle accettrici rivestite con anticorpo anti-fosfotirosina PY100. Come substrato viene utilizzato poli(Glu,Tyr) 4:1 biotinilato. La fosforilazione del substrato viene misurata mediante l'aggiunta di perle donatrici/accettrici per luminescenza dopo la formazione del complesso perla donatrice-accettrice. La Protein Tyrosine Kinase e i composti di prova vengono combinati e preincubati per 60 minuti, seguiti dall'aggiunta di ATP e poli(Glu, Tyr) biotinilato in un volume totale di 20 μL in piastre per microtitolazione bianche a 384 pozzetti con legame medio (Greiner). Le miscele di reazione vengono incubate per 1 ora a temperatura ambiente. Le reazioni vengono bloccate mediante l'aggiunta di 10 μL di sospensione di perle AlphaScreen da 15-30 μg/mL contenente 75 mM Hepes, pH 7,4, 300 mM NaCl, 120 mM EDTA, 0,3% BSA e 0,03% Tween-20. Dopo 2-16 ore di incubazione a temperatura ambiente, le piastre vengono lette utilizzando un lettore AlphaQuest.
In vivo	Una singola dose orale di 100 mg/kg di XL880 tramite gavage orale determina una sostanziale inibizione della fosforilazione di Met tumorale B16F10 e della fosforilazione del recettore indotta da ligandi (ad es. HGF o VEGF) di Met nel fegato e di Flk-1/KDR nel polmone, entrambe persistenti per 24 ore. Il trattamento con XL880 (30-100 mg/kg, una volta al giorno, gavage orale) determina una riduzione del carico tumorale. Il carico tumorale superficiale polmonare è ridotto del 50% e del 58% in seguito al trattamento rispettivamente con 30 e 100 mg/kg di XL880. Il trattamento con XL880 di topi portatori di tumori solidi B16F10 determina anche un'inibizione dose-dipendente della crescita tumorale del 64% e dell'87% rispettivamente a 30 e 100 mg/kg. Per entrambi gli studi, la somministrazione di XL880 è stata ben tollerata senza significativa perdita di peso corporeo. XL880 è sviluppato per bersagliare la segnalazione anormale di HGF tramite Met e contemporaneamente bersagliare diverse Protein Tyrosine Kinases recettoriali coinvolte nell'angiogenesi tumorale. XL880 ha causato emorragia tumorale e necrosi in xenotrapianti umani entro 2-4 ore, e la necrosi tumorale massima è stata osservata a 96 ore (dopo cinque dosi giornaliere), con conseguente regressione completa.
Riferimenti	[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/

Applicazioni

Metodi	Biomarcatori	Immagini	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

Informazioni sullo studio clinico

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
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

Supporto tecnico

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