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Tivantinib c-Met inhibitor

Name: Tivantinib
Brand: Selleck Chemicals
SKU: S2753
Rating: 5 (49 reviews)

Kat.-Nr.: S2753

Tivantinib is the first non-ATP-competitive c-Met inhibitor with K_i of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. This compound induces a G2/M arrest and apoptosis.

Tivantinib c-Met inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 369.42

Springe zu

Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.65%

99.65

Verwandte Ziele	EGFR VEGFR FGFR PDGFR Src MEK CSF-1R HER2 FLT3 c-Kit
Weitere c-Met Inhibitoren	Tepotinib (EMD-1214063) Dihexa SGX-523 PHA-665752 Foretinib (GSK1363089, XL880) SU11274 BMS-777607 JNJ-38877605 PF-04217903 Savolitinib (AZD6094)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien	Assay-Typ	Konzentration	Formulierung	Aktivitätsbeschreibung
MNK-45	Kinase assay	~10 μM		inhibits c-Met phosphorylation and downstream c-Met signaling pathways
HT29	Kinase assay	~10 μM		inhibits c-Met phosphorylation and downstream c-Met signaling pathways
MDA-MB-231	Kinase assay	~10 μM		inhibits c-Met phosphorylation and downstream c-Met signaling pathways
NCI-H441	Kinase assay	~10 μM		inhibits c-Met phosphorylation and downstream c-Met signaling pathways
SK-MEL-28	Growth inhibitory assay	33 μM		IC50>33 μM
NCI-H661	Growth inhibitory assay	33 μM		IC50>33 μM
NCI-H446	Growth inhibitory assay	33 μM		IC50=7 μM
MDA-MB-231	Growth inhibitory assay	33 μM		IC50=0.55 μM
DLD-1	Growth inhibitory assay	33 μM		IC50=0.53 μM
A549	Growth inhibitory assay	33 μM		IC50=0.59 μM
SK-OV-3	Growth inhibitory assay	33 μM		IC50=0.66 μM
NCI-H460	Growth inhibitory assay	33 μM		IC50=0.6 μM
A375	Growth inhibitory assay	33 μM		IC50=0.42 μM
NCI-H441	Growth inhibitory assay	33 μM		IC50=0.3 μM
HT29	Growth inhibitory assay	33 μM		IC50=0.49 μM
MKN-45	Growth inhibitory assay	33 μM		IC50=0.58 μM
HT29	Apoptosis assay	~10 μM		significantly induces apoptosis by 80-90%.
MKN-45	Apoptosis assay	~10 μM		significantly induces apoptosis by 80-90%.
MDA-MB-231	Apoptosis assay	~10 μM		modestly induces apoptosis by 35%.
MDA-MB-231/TGL	Growth inhibitory assay	~100 μM		GI50=1.2 μM
1833/TGL	Growth inhibitory assay	~100 μM		GI50=3.7 μM
EBC1	Cytotoxic assay	~10 μM		inhibits the cell growth.
SNU638	Cytotoxic assay	~10 μM		inhibits the cell growth.
A549	Cytotoxic assay	~10 μM		not affect
H460	Cytotoxic assay	~10 μM		not affect
HCC827	Cytotoxic assay	~10 μM		not affect
A549	Function assay	10 μM		disrupts microtubule
EBC1	Function assay	10 μM		disrupts microtubule
H460	Function assay	10 μM		inhibits tubulin polymerization
K562/VCR	Cytotoxic assay	~10 μM		shows cytotoxic activity
CEM/VBL	Cytotoxic assay	~10 μM		shows cytotoxic activity
U266	Cytotoxic assay	~3 μM		IC50=1.1 μM
OPM-2	Cytotoxic assay	~3 μM		IC50=1.8 μM
MM.1S	Cytotoxic assay	~3 μM		IC50=1.6 μM
MM.1R	Growth inhibitory assay	3 μM		inhibits cell growth by 49%
RPMI-8226	Cytotoxic assay	~3 μM		IC50=0.9 μM
ANBL-6	Cytotoxic assay	1 μM		induces cell death by more than 50%
ANLB-6/V10R	Cytotoxic assay	1 μM		induces cell death by more than 50%
KAS-6/1	Cytotoxic assay	1 μM		induces cell death by more than 50%
KAS-6/V10R	Cytotoxic assay	1 μM		induces cell death by more than 50%
KAS-6/R10R	Cytotoxic assay	1 μM		induces cell death by more than 50%
8226/S	Growth inhibitory assay	3 μM		inhibits cell growth by 54%
8226/LR-5	Growth inhibitory assay	3 μM		inhibits cell growth by 54%
Huh7	Cytotoxic assay	~4.8 μM	DMSO	IC50=9.9 nM
Hep3B	Cytotoxic assay	~4.8 μM	DMSO	IC50=448.7 nM
HepG2	Cytotoxic assay	~4.8 μM	DMSO	IC50=139.77 nM
Chang	Cytotoxic assay	~4.8 μM	DMSO	IC50=448.7 nM
Huh7	Function assay	1.6 μM	DMSO	causes a G2/M cell cycle arrest
Hep3B	Function assay	1.6 μM	DMSO	causes a G2/M cell cycle arrest
HepG2	Function assay	1.6 μM	DMSO	causes a G2/M cell cycle arrest
Chang	Function assay	1.6 μM	DMSO	causes a G2/M cell cycle arrest
MHCC97L	Growth inhibitory assay	~10 μM	DMSO	IC50=315 nM
MHCC97H	Growth inhibitory assay	~10 μM	DMSO	IC50=368 nM
Huh7	Growth inhibitory assay	~10 μM	DMSO	IC50=265 nM
HepG2	Growth inhibitory assay	~10 μM	DMSO	IC50=392 nM
MHCC97L	Function assay	1 μM	DMSO	induces microtubules depolymerization
Huh7	Function assay	1 μM	DMSO	induces microtubules depolymerization
MHCC97L	Apoptosis assay	1 μM	DMSO	induces apoptosis
Huh7	Apoptosis assay	1 μM	DMSO	induces apoptosis
C3H 10T1/2 mouse fibroblasts	Kinase assay	25 μM	DMSO	reduces Histone H3 and H4 acetylation levels
H23	Growth inhibitory assay	25 μM	DMSO	significantly inhibits cell growth.
WM35	Growth inhibitory assay	10 μM	DMSO	significantly inhibits cell growth.
NIH 3T3	Growth inhibitory assay	10 μM	DMSO	does not have a significant inhibitory effect
H838	Growth inhibitory assay	10 μM	DMSO	does not have a significant inhibitory effect
H1395	Growth inhibitory assay	10 μM	DMSO	does not have a significant inhibitory effect
Quiescent S2	Kinase assay	30 μM	DMSO	completely abrogates TSA-induced hyperacetylation of H3K4me3 histones
PC3	Apoptosis assay	20 μM	DMSO	induces apoptosis
Du145	Apoptosis assay	20 μM	DMSO	induces apoptosis
LNCaP	Apoptosis assay	20 μM	DMSO	induces apoptosis
LAPC-4	Apoptosis assay	20 μM	DMSO	induces apoptosis
LNCaP	Function assay	20 μM	DMSO	decreases PSA secretion and p65 expression levels
LAPC-4	Function assay	20 μM	DMSO	decreases PSA secretion and p65 expression levels
Kasumi-1	Growth inhibitory assay	~50 μM	DMSO	inhibits cell proliferation
SKNO-1	Growth inhibitory assay	~50 μM	DMSO	inhibits cell proliferation
Kasumi-1	Kinase assay	~10 μM	DMSO	reduces expression of acetylated histone H3, c-kit and bcl-2
SKNO-1	Kinase assay	~10 μM	DMSO	reduces expression of acetylated histone H3, c-kit and bcl-2
A549	Function assay	10 μM	DMSO	enhances mitotic catastrophe
NRK-52E	Function assay	10 μM	DMSO	inhibits Ang II-induced STAT3 nuclear translocation and the expression of TGF-β1, collagen IV and fibronectin
PC12	Growth inhibitory assay	~12.5 μM	DMSO	prevents TSA-induced neurite formation
HPMCs	Function assay			reverses epithelial to mesenchymal transition of human peritoneal mesothelial cells
A549	Function assay	~50 μM	DMSO	affects the viral life cycle and host response
RAW264.7	Function assay	~30 μM	DMSO	reduces pro-inflammatory gene expression
MEMM	Kinase assay	15 µM	DMSO	decreases acetylation of histone H3
MEMM	Growth inhibitory assay	~20 µM	DMSO	inhibits cell proliferation
MEMM	Apoptosis assay	15 µM	DMSO	induces the presence of the apoptosis protein, cleaved Caspase-3
T47D	Growth inhibitory assay	10 μM	DMSO	IC50=72 nM
ZR-75-1	Growth inhibitory assay	10 μM	DMSO	IC50=79 nM
BT474	Growth inhibitory assay	10 μM	DMSO	IC50=86 nM
HCC1954	Growth inhibitory assay	10 μM	DMSO	IC50=119 nM
MDA-MB-453	Growth inhibitory assay	10 μM	DMSO	IC50=975 nM
MDA-MB-468	Growth inhibitory assay	10 μM	DMSO	IC50=3208 nM
SkBr3	Growth inhibitory assay	10 μM	DMSO	IC50>10,000 nM
MDA-MB-231	Growth inhibitory assay	10 μM	DMSO	IC50>10,000 nM
HCT116	Growth inhibitory assay	10 μM	DMSO	IC50=5836 nM
HT29	Growth inhibitory assay	10 μM	DMSO	IC50>10,000 nM
HFF	Growth inhibitory assay	10 μM	DMSO	IC50=7615 nM
HN5	Growth inhibitory assay	10 μM	DMSO	IC50>10,000 nM
786-0	Growth inhibitory assay	10 μM	DMSO	IC50=4009 nM
H157	Growth inhibitory assay	10 μM	DMSO	IC50=2642 nM
NCI-H460	Growth inhibitory assay	10 μM	DMSO	IC50>2,500 nM
SKOV-3	Growth inhibitory assay	10 μM	DMSO	IC50=2126 nM
OVCAR-3	Growth inhibitory assay	10 μM	DMSO	IC50=2918 nM
BXPC3	Growth inhibitory assay	10 μM	DMSO	IC50=3141 nM
MiaPaCa	Growth inhibitory assay	10 μM	DMSO	IC50=5433 nM
PANC-1	Growth inhibitory assay	10 μM	DMSO	IC50=8681 nM
LNCaP	Growth inhibitory assay	10 μM	DMSO	IC50=147 nM
DU145	Growth inhibitory assay	10 μM	DMSO	IC50=3812 nM
PC3	Growth inhibitory assay	10 μM	DMSO	IC50>10,000 nM
BT474	Kinase assay	10 μM	DMSO	inhibits pGSK3β with IC50 of 160 nM
786-0	Kinase assay	10 μM	DMSO	inhibits pGSK3β with IC50 of 150 nM
LNCaP	Kinase assay	10 μM	DMSO	inhibits pGSK3β with IC50 of 43 nM
PC3	Kinase assay	10 μM	DMSO	inhibits pGSK3β with IC50 of 49 nM
KARPAS-231	Growth inhibitory assay	10 μM	DMSO	EC50=41 nM
CCRFSB	Growth inhibitory assay	10 μM	DMSO	EC50=155 nM
SUP B15	Growth inhibitory assay	10 μM	DMSO	EC50=197 nM
SD-1	Growth inhibitory assay	10 μM	DMSO	EC50=320 nM
RS4;11	Growth inhibitory assay	10 μM	DMSO	EC50=654 nM
MN-60	Growth inhibitory assay	10 μM	DMSO	EC50=3602 nM
Tanoue	Growth inhibitory assay	10 μM	DMSO	EC50=4517 nM
RCH-ACV	Growth inhibitory assay	10 μM	DMSO	EC50=152 nM
SEM	Growth inhibitory assay	10 μM	DMSO	EC50=202 nM
KASUMI-2	Growth inhibitory assay	10 μM	DMSO	EC50=225 nM
REH	Growth inhibitory assay	10 μM	DMSO	EC50=288 nM
697	Growth inhibitory assay	10 μM	DMSO	EC50=338 nM
NALM-6	Growth inhibitory assay	10 μM	DMSO	EC50=421 nM
MHH-CALL–3	Growth inhibitory assay	10 μM	DMSO	EC50=812 nM
MHH-CALL–2	Growth inhibitory assay	10 μM	DMSO	EC50=2114 nM
J.GAMMA-1	Growth inhibitory assay	10 μM	DMSO	EC50=65 nM
JR45.01	Growth inhibitory assay	10 μM	DMSO	EC50=68 nM
A3	Growth inhibitory assay	10 μM	DMSO	EC50=69 nM
I 2.1	Growth inhibitory assay	10 μM	DMSO	EC50=73 nM
MOLT-3	Growth inhibitory assay	10 μM	DMSO	EC50=74 nM
P116	Growth inhibitory assay	10 μM	DMSO	EC50=78 nM
J.Cam1.6	Growth inhibitory assay	10 μM	DMSO	EC50=79 nM
I 9.2	Growth inhibitory assay	10 μM	DMSO	EC50=80 nM
LOUCY	Growth inhibitory assay	10 μM	DMSO	EC50=117 nM
J.RT3-T3.5	Growth inhibitory assay	10 μM	DMSO	EC50=123 nM
800000	Growth inhibitory assay	10 μM	DMSO	EC50=163 nM
Jurkat	Growth inhibitory assay	10 μM	DMSO	EC50=225 nM
MOLT-4	Growth inhibitory assay	10 μM	DMSO	EC50=232 nM
Molt-16	Growth inhibitory assay	10 μM	DMSO	EC50=241 nM
CEM/C3	Growth inhibitory assay	10 μM	DMSO	EC50=257 nM
CEM/C2	Growth inhibitory assay	10 μM	DMSO	EC50=271 nM
CCRFCEM	Growth inhibitory assay	10 μM	DMSO	EC50=327 nM
CEM/C1	Growth inhibitory assay	10 μM	DMSO	EC50=382 nM
SUPTI[VB]	Growth inhibitory assay	10 μM	DMSO	EC50=619 nM
CCRF–HSB-2	Growth inhibitory assay	10 μM	DMSO	EC50=2117 nM
I 2.1	Apoptosis assay	10 μM	DMSO	induces apoptosis
I 9.2	Apoptosis assay	10 μM	DMSO	induces apoptosis
A3	Apoptosis assay	10 μM	DMSO	induces apoptosis
RD	Growth inhibitory assay	10 μM		IC50>10 μM
Rh41	Growth inhibitory assay	10 μM		IC50=33.8 nM
Rh18	Growth inhibitory assay	10 μM		IC50=303 nM
Rh30	Growth inhibitory assay	10 μM		IC50=4.81 μM
BT-12	Growth inhibitory assay	10 μM		IC50>10 μM
CHLA-266	Growth inhibitory assay	10 μM		IC50=1.22 μM
TC-71	Growth inhibitory assay	10 μM		IC50=2.52 μM
CHLA-9	Growth inhibitory assay	10 μM		IC50=591 nM
CHLA-10	Growth inhibitory assay	10 μM		IC50=102 nM
CHLA-258	Growth inhibitory assay	10 μM		IC50=1.05 μM
GBM2	Growth inhibitory assay	10 μM		IC50=9.15 μM
NB-1643	Growth inhibitory assay	10 μM		IC50=5.4 μM
NB-Ebc1	Growth inhibitory assay	10 μM		IC50>10 μM
CHLA-90	Growth inhibitory assay	10 μM		IC50>10 μM
CHLA-136	Growth inhibitory assay	10 μM		IC50>10 μM
NALM-6	Growth inhibitory assay	10 μM		IC50=265 nM
COG-LL-317	Growth inhibitory assay	10 μM		IC50=6.49 nM
RS4;11	Growth inhibitory assay	10 μM		IC50=147 nM
MOLT-4	Growth inhibitory assay	10 μM		IC50=40 nM
CCRF-CEM	Growth inhibitory assay	10 μM		IC50=268 nM
Kasumi-1	Growth inhibitory assay	10 μM		IC50=107 nM
Karpas-299	Growth inhibitory assay	10 μM		IC50=2.93 μM
Ramos-RA1	Growth inhibitory assay	10 μM		IC50=7.35 μM
H1299	Kinase assay	10 μM		inhibits IKBKE-induced Akt Activation
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht	369.42	Formel	C₂₃H₁₉N₃O₂	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	905854-02-6	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	ARQ 197			Smiles	C1CC2=C3C(=CC=C2)C(=CN3C1)C4C(C(=O)NC4=O)C5=CNC6=CC=CC=C65

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 73 mg/mL (197.6 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 35 mg/mL

Water : Insoluble

DMSO : 74 mg/mL (200.31 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 74 mg/mL

Water : Insoluble

DMSO : 74 mg/mL (200.31 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 40 mg/mL

Water : Insoluble

DMSO : 73 mg/mL (197.6 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 12 mg/mL

Water : Insoluble

DMSO : 73 mg/mL (197.6 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	5%DMSO 1 Corn oil Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	3.500mg/ml (9.47mM)	Taking the 1 mL working solution as an example, add 50 μL of 70 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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 (Mechanism of Action)

Merkmale	The first selective c-Met inhibitor to be advanced into human clinical trials.
Targets/IC₅₀/Ki	c-Met (Cell-free assay) 0.355 μM(Ki)
In vitro	ARQ-197 has been shown to prevent HGF/c-met induced cellular responses in vitro. This compound possesses antitumor activity; inhibiting proliferation of A549, DBTRG and NCI-H441 cells with IC50 of 0.38, 0.45, 0.29 μM. Treatment with this agent results in a decrease in phosphorylation of the MAPK signaling cascade and prevention of invasion and migration. In addition, ectopic expression of c-Met in NCI-H661, a cell line having no endogenous expression of c-Met, causes it to acquire an invasive phenotype that is also suppressed by this chemical. Although the addition of increasing concentrations of this inhibitor does not significantly affect the K_m of ATP, exposure of c-Met to 0.5 μM of this substance decreased the V_max of c-Met by approximately 3-fold. The ability of this molecule to decrease the V_max without affecting the Km of ATP confirmed that it inhibits c-Met through a non–ATP-competitive mechanism and may therefore account for its high degree of kinase selectivity. It prevents human recombinant c-Met with a calculated inhibitory constant K_i of approximately 355 nM. Although the highest concentration of ATP used is 200 μM, the potency of this compound against c-Met is not reduced by using concentrations of ATP up to 1 mM. It blocks c-Met phosphorylation and downstream c-Met signaling pathways. This chemical suppresses constitutive and ligand-mediated c-Met autophosphorylation and, by extension, c-Met activity, in turn leading to the inhibition of downstream c-Met effectors. Its induction of caspase-dependent apoptosis is increased in c-Met–expressing human cancer cells including HT29, MKN-45, and MDA-MB-231 cells.
Kinase-Assay	c-Met SDS-PAGE In-vitro-Kinase-Assay
Kinase-Assay	Rekombinantes c-Met-Protein (100 ng) wird 30 Minuten bei Raumtemperatur mit steigenden Konzentrationen dieser Verbindung vorinkubiert. Nach der Vorinkubation werden 100 μM Poly-Glu-Tyr-Substrat und verschiedene ATP-Konzentrationen, die 5 μCi [γ-32P]ATP enthalten, der Reaktionsmischung zugesetzt. Die Reaktion wird 5 Minuten bei Raumtemperatur inkubiert und dann durch Zugabe von 5 μL SDS-Polyacrylamidgel, reduzierendem Probenpuffer, gestoppt. Die Proben werden dann auf ein 7,5%iges Acrylamidgel geladen und eine SDS-PAGE durchgeführt. Die phosphorylierten Poly-Glu-Tyr-Substrate werden schließlich durch Autoradiographie sichtbar gemacht. Die c-Met-Aktivität wird durch Densitometrie quantifiziert.
In vivo	All three xenograft models treated with Tivantinib display reductions in tumor growth: 66% in the HT29 model, 45% in the MKN-45 model, and 79% in the MDA-MB-231 model. In these xenograft studies, no significant body weight changes following oral administration of this compound at 200 mg/kg are observed. Pharmacodynamically, the phosphorylation of c-Met in human colon xenograft tumors (HT29) is strongly inhibited by this chemical, as assessed by a dramatic reduction of c-Met autophosphorylation 24 hours after a single oral dose of 200 mg/kg of this agent. This same dosage in mice exhibits that tumor xenografts are exposed to sustained plasma levels of the compound, consistent with the observed pharmacodynamic inhibition of c-Met phosphorylation and inhibition of proliferation of c-Met harboring cancer cell lines. Plasma levels of the agent 10 hours after dosing are determined to be 1.3 μM, more than 3-fold above the biochemical inhibitory constant of this substance for c-Met. Therefore, it is able to suppress its target in vivo in the xenografted human tumor tissue. In conclusion, this inhibitor blocks the growth of c-Met-dependent xenografted human tumors.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/20484018/ [2] https://pubmed.ncbi.nlm.nih.gov/18511928/

Anwendungen (Applications)

Methoden	Biomarker	Bilder	PMID
Western blot	cMET / p-cMET / p-AKT / p-ERK / p-rpS6		23022995
Growth inhibition assay	Cell viability		23598276

Klinische Studieninformationen (Clinical Trial Information)

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

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
NCT02150733	Completed	Hepatic Impairment\|Solid Tumor\|Cancer	Daiichi Sankyo\|Medpace Inc.	April 2014	Phase 1
NCT01892527	Completed	Colorectal Cancer Metastatic\|C-met Overexpression	Armando Santoro MD\|Istituto Clinico Humanitas	March 2013	Phase 2
NCT02049060	Completed	Malignant Pleural Mesothelioma\|Nonsquamous Nonsmall Cell Neoplasm of Lung	Armando Santoro MD\|Istituto Clinico Humanitas	January 2013	Phase 1\|Phase 2
NCT01755767	Completed	Hepatocellular Carcinoma	Daiichi Sankyo\|ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)	December 27 2012	Phase 3

Häufig gestellte Fragen (Frequently Asked Questions)

Frage 1:
Are there any other solutions (apart from DMSO) I can dissolve it for in vivo experiment?

Antwort:
S2753 This compound (ARQ 197) can be dissolved in 1% methylcellulose at 15 mg/ml as a suspension.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Tivantinib c-Met inhibitor

Chemische Struktur

Molekulargewicht: 369.42

Qualitätskontrolle (Quality Control)

Zellkultur, Behandlung & Arbeitskonzentration (Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkmechanismus (Mechanism of Action)

Anwendungen (Applications)

Klinische Studieninformationen (Clinical Trial Information)

Häufig gestellte Fragen (Frequently Asked Questions)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)