Home Protein Tyrosine Kinase EGFR Inhibitor AG-490

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AG-490 EGFR Inhibitor

Kat.-Nr.: S1143

AG-490 ist ein Inhibitor von EGFR mit einem IC50 von 0,1 μM in zellfreien Assays, 135-fach selektiver für EGFR gegenüber ErbB2, hemmt auch JAK2 ohne Aktivität gegenüber Lck, Lyn, Btk, Syk und Src.
AG-490 EGFR Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 294.30

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.99%
99.99

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

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
BC3 Function Assay 100 µM 24 h mediates PEL cell apoptosis
BCBL1 Function Assay 100 µM 24 h mediates PEL cell apoptosis
BC3 Function Assay 100 µM 24 h mediates de-phosphorylation of STAT3 correlated with HSP70 and HSF1 reduction
BCBL1 Function Assay 100 µM 24 h mediates de-phosphorylation of STAT3 correlated with HSP70 and HSF2 reduction
BC3 Function Assay 100 µM 24 h induces a complete autophagic flux 
BCBL1 Function Assay 100 µM 24 h induces a complete autophagic flux 
SK-MEL-28 Function Assay 50/100 µM 48 h DMSO reduces anoikis resistance
MeWo Function Assay 50/100 µM 48 h DMSO reduces anoikis resistance
SK-MEL-5 Function Assay 50/100 µM 48 h DMSO reduces anoikis resistance
SK-MEL-2 Function Assay 50/100 µM 48 h DMSO reduces anoikis resistance
B16-F0 Function Assay 50/100 µM 48 h DMSO reduces anoikis resistance
TRPM2/HEK  Function Assay 0.1–25 µM 15 min DMSO reduces H2O2-induced Ca2+increase in a concentration-dependent manner, and the IC50 value was 1.7 µM
U937  Function Assay 0.1–25 µM 15 min DMSO reduces H2O2-induced Ca2+increase in a concentration-dependent manner, and the IC50 value was 0.4 µM
TRPM2/HEK  Function Assay 10 µM 40 min DMSO reduces TRPM2 activation even at high concentrations of H2O2
GL37  Cell Viability Assay 0-10 µM 48 h suppresses La expression
NRK-52E Function Assay 1 µM 10 min blocks the stimulatory effect of Ang II on Pax-2 expression 
NRK-52E Function Assay 1 µM 10 min blocks Ang II induced CD24 expression
HSC  Function Assay 20 μM 1 h abrogates the differential effects of leptin or AGEs
EJ Growth Inhibition Assay 50/80 μM 24/48/72 h inhibits cell growth in both time and dose dependent manner
EJ Growth Inhibition Assay 50/80 μM 48 h causes S-phase arrest
EJ Function Assay 50/80 μM 48 h downregulates c-Myc, cyclinD1, survivin and VEGF expressions
HepG2 Function Assay 50-500 μM 60 min inhibits the IL-6-induced phosphorylation of STAT1 (Tyr705) and STAT3 (Tyr705) in a dose-dependent manner
SGC7901 Cell Viability Assay 0-100 μM 24/48/72 h causes a significant reduction in cell viability dose-dependently but not time-dependently
AGS  Cell Viability Assay 0-100 μM 24/48/72 h causes a significant reduction in cell viability dose-dependently but not time-dependently
SGC7901 Function Assay 50 μM 24/48/72 h the levels of pJAK2 began to decline at 24 hr, and rebounded at 72 hr 
AGS  Function Assay 50 μM 24/48/72 h the levels of pJAK2 began to decline at 24 hr, and rebounded at 72 hr 
SGC7901 Function Assay 50 μM 24/48/72 h the cytoplasmic localization of pJAK2 (JAK2 phosphorylated at residues Tyr1007 and Tyr1008) decreased after AG490 treatment for 24 and 48 hr, but started to rebound at 72 hr
AGS  Function Assay 50 μM 24/48/72 h the cytoplasmic localization of pJAK2 (JAK2 phosphorylated at residues Tyr1007 and Tyr1008) decreased after AG490 treatment for 24 and 48 hr, but started to rebound at 72 hr
MC3T3-E1  Function Assay 50 μM 4 h inhibits HSE-induced BMP7 and GHR protein expression 
7TD1-DXM Growth Inhibition Assay 10 μM 72 h DMSO inhibits cell growth
7TD1-WD-90 Growth Inhibition Assay 10 μM 72 h DMSO inhibits cell growth
7TD1-DXM Apoptosis Assay 50 μM 48 h DMSO induces apoptosis
7TD1-WD-90 Apoptosis Assay 50 μM 48 h DMSO induces apoptosis
7TD1-WD-90  Function Assay 50 μM 6 h DMSO significantly inhibits the phosphorylation of JAK2 and phosphorylation of STAT3
HepG2  Function Assay 100 μM 12/24 h inhibits STAT3 tyrosine phosphorylation
RAW264.7  Function Assay 50 μM  24/48 h suppresses RANKL-induced osteoclastogenesis
RAW264.7 Growth Inhibition Assay 0-50 μM  48 h inhibits cell growth dose-dependently
RAW264.7 Growth Inhibition Assay 0-50 μM  48 h causes an arrest of RAW264.7 cells at the G0/G1 phase of the cell cycle
RAW264.7 Function Assay 50 μM 24/48 h inhibits RANKL-induced NFATc1 expression and phosphorylation of Ser727STAT3
A549  Function Assay 20/40 μM 20 h 20 μM AG490 suppresses the radiation-induced invasion of A549 cells
A549  Function Assay 10/20/40 μM 24 h suppresses the radiation-induced elevation of VEGF 
HUVECs Cell Viability Assay 20 µM 4 h attenuates H2O2-induced cell shrinkage and improved the attachment rate of the cells
HUVECs Apoptosis Assay 20 µM 4 h significantly decreases the cell apoptotic index
BV-2  Function Assay 20 µM 16 h inhibits LPS-induced STAT1 phosphorylation with almost completely diminished iNOS expression
NRK-52E  Function Assay 5 μM 30 min attenuates Ang-(1–7)-inhibited TGF-β1 mRNA at 16 h 
SW620  Function Assay 20 µM 1/6 h inhibits p-STAT3 activation
RPE  Function Assay 30 µM  3 h inhibits the induction of p-STAT3 expression
SW1116 Function Assay 100 µM  24/48/72 h decreases the expression of JAK2 and pJAK2 time-dependently
HT29 Function Assay 100 µM  24/48/72 h decreases the expression of JAK2 and pJAK2 time-dependently
SW1116 Function Assay 100 µM  24/48/72 h decreases the pSTAT3 levels in a time-dependent manner 
HT29 Function Assay 100 µM  24/48/72 h decreases the pSTAT3 levels in a time-dependent manner 
ARPE-19 Function Assay 5 μM 30 min inhibits JAK2 phosphorilation
HSC-T6 Apoptosis Assay 10 μM 2 h  inhibits the apoptosis of HSC-T6 cells induced by CDE
HSC-T6 Function Assay 10 μM 2 h  inhibits the expressions of pY-STAT1 and Bad induced by CDE
Hep-2 Growth Inhibition Assay 25-100 μM 24/48/72 h inhibits cell growth in both time and dose dependent manner
Hep-2 Apoptosis Assay 50 μM 24/48/72 h induces cell apoptosis time dependently
Hep-2 Function Assay 50 μM 24/48/72 h inhibits G1 to S cell cycle transition and induces G1 cell cycle arrest
Hep-2 Function Assay 50 μM 24/48/72 h downregulates the STAT3, p-STAT3 and survivin protein levels
KF8 Function Assay 10 μM  1 h DMSO  inhibits IL-33-induced NF-κB activation
KF8 Function Assay 10 μM  1 h  DMSO  inhibits IL-33-induced IκBα degradation and NF-κB activation
HEL  Function Assay 100 μM 12-72 h inhibits the level of p-JAK2, JAK2
HEL Growth Inhibition Assay 100 μM 0-5 d reduces growth of JAK2V617F-expressing HEL cells
A-172 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-18 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-54 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-256 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-304 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
A-172 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-18 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-54 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-256 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-304 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
A-172 Function Assay 50/100 μM 48 h inhibits migration
MZ-18 Function Assay 50/100 μM 48 h inhibits migration
MZ-54 Function Assay 50/100 μM 48 h inhibits migration
MZ-256 Function Assay 50/100 μM 48 h inhibits migration
MZ-304 Function Assay 50/100 μM 48 h inhibits migration
A-172 Function Assay 100 μM 48 h inhibits invasion
MZ-18 Function Assay 100 μM 48 h inhibits invasion
MZ-54 Function Assay 100 μM 48 h inhibits invasion
MZ-256 Function Assay 100 μM 48 h inhibits invasion
MZ-304 Function Assay 100 μM 48 h inhibits invasion
A-172 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-18 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-54 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-256 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-304 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
SW1990 Growth Inhibition Assay 20 μM 24/48/72 h inhibits cell growth time dependently
SW1990 Function Assay 20 μM 24 h decreases the expression of MMP-2 and VEGF mRNAs
SW1990 Function Assay 20 μM 24 h decreases the intensity of p-Stat3 expression
SW1990 Invasion Assay 20 μM 24 h reduces invasion of SW1990 cells 
THP1 Function Assay 10 uM 30 min  inhibits STAT3 tyrosine phosphorylation by over 60%
BMMC Function Assay 0-10 μM 15 min inhibits LTC4 release in a dose-dependent fashion with near complete inhibition at concentrations ⩾10 μM
A549 Function Assay 15 μm 1 h inhibits the phosphorylation of STAT1 on tyrosine 701 was detected 15 min after SPE B treatment
OVCAR-3 Function Assay 10 uM 1 h inhibits LPA-induced STAT3 phosphorylation
PA-1 Function Assay 10 uM 1 h inhibits LPA-induced STAT3 phosphorylation
OVCAR-3 Function Assay 10 uM 1 h inhibits LPA-induced ovarian cancer cell motility
PA-1 Function Assay 10 uM 1 h inhibits LPA-induced ovarian cancer cell motility
Jurkat  Growth Inhibition Assay 50 μM 24/48/72 h enhances TRAIL-induces cell growth inhibition
SUPT1  Growth Inhibition Assay 50 μM 24/48/72 h enhances TRAIL-induces cell growth inhibition
Jurkat  Apoptosis Assay 50 μM 24/48 h enhances TRAIL-induces cell apoptosis
SUPT1  Apoptosis Assay 50 μM 24/48 h enhances TRAIL-induces cell apoptosis
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

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

Molekulargewicht 294.30 Formel

C17H14N2O3

 Lagerung (Ab dem Eingangsdatum)
CAS-Nr. 133550-30-8 SDF herunterladen Lagerung von Stammlösungen

Synonyme Tyrphostin B42, Zinc02557947 Smiles C1=CC=C(C=C1)CNC(=O)C(=CC2=CC(=C(C=C2)O)O)C#N

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 58 mg/mL (197.07 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 9 mg/mL

Water : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewichtsrechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

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

mg/kg g μL

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)

Targets/IC50/Ki
JAK2 (V617F)
EGFR
(Cell-free assay)
0.1 μM
In vitro

AG-490 inhibits HER-2 driven cell proliferation with IC50 of 3.5 μM. Corresponding to the specific dose-dependent inhibition of constitutively activated JAK2 in pre-B acute leukemia (ALL) cells, this compound (5 μM) almost completely blocks the growth of all ALL cells by inducing programmed cell death, with no deleterious effect on normal hematopoiesis. This chemical does not inhibit the activities of Lck, Lyn, Btk, Syk, and Src. It (60-100 μM) blocks the constitutive activation of Stat3sm, and inhibits spontaneous as well as interleukin 2-induced growth of mycosis fungoides (MF) tumor cells with IC50 values of 75 μM and 20 μM, respectively. This compound potently inhibits IL-2-mediated human T cell growth with an IC50 of 25 μM by blocking the activities of JAK3 and STAT5a/b. It significantly inhibits the constitutive activation of Stat3 in MOPC, MPC11, and S194 cells, leading to dramatic dose-dependent apoptosis. This chemical (100 μM) inhibits Akt phosphorylation, inhibits the activation of nuclear factor-κB, and causes the activation of GSK-3β, leading to the reduction of c-Myc. It (50 μM) can induce apoptosis of BaF3 cells expressing T315I and E255K mutants of Bcr-Abl. This compound at 30 μM inhibits not only Epo-induced phosphorylation of wild-type JAK2 but also constitutive phosphorylation of the JAK2 V617F mutant. It also potently inhibits cytokine-independent cell growth induced by the JAK2 V617F mutant in BaF3 cells.

Kinase-Assay
In-vitro-Kinase-Autophosphorylierung
AG-490 wird in DMSO 10%-H2O-Ethanol 45% gelöst. Rohe Membranextrakte (0,125 μg/mL) werden mit EGF (20 nM) in 50 mM HEPES-Puffer, pH 7,6, und 125 mM NaCl, 15 Minuten bei 4 °C voraktiviert. Die Autophosphorylierungsaktivität der EGFR- oder ErbB2-Kinase wird bei 4 °C für 30 Sekunden in V-förmigen 96-Well-Platten getestet. Membranextrakte (8 μL) werden zu jeder Vertiefung mit Reaktionsgemisch (12 μL, 50mM, HEPES, pH 7,4, 125 mM NaCl, 12 mM M8Ac2, 2 mM MnCl2, 1 mM NaVO3, 1 μM ATP und 1 μCi[γ-32P]ATP, Endkonzentrationen) und zunehmenden Konzentrationen dieser Verbindung (4 μL) gegeben. Nach Beendigung durch Zugabe von heißem Probenpuffer werden die Proben auf einer 6%igen SDS-Polyacrylamidgel-Elektrophorese-Minigel aufgetragen, die Gele getrocknet und eine Autoradiographie während der linearen Expositionszeit durchgeführt. Die Rezeptorbanden werden densitometrisch gescannt und die Ergebnisse mit dem Ez-Fit-Programm analysiert. Zur Analyse der Autophosphorylierung von JAK2 wird JAK2 mittels Anti-JAK2-Antikörper aus Lysaten von G2-Zellen immunpräzipitiert, die 16 Stunden lang mit zunehmenden Konzentrationen dieser Chemikalie (0-50 μM) vorbehandelt wurden. Immunkomplexe werden dann mit Anti-Phosphotyrosin-Antikörpern immungeblottet. Eine dosisabhängige Hemmung der In-vitro-Kinaseaktivität wird durch Bewertung der JAK2-Autophosphorylierung nachgewiesen.
In vivo

Administration of AG-490 drastically reduces the numbers of CD45+ and HLA-DR+ cells from 48 % and 46% in bone marrow of untreated mice, as well as 38% and 22% in the spleen of untreated mice to undetectale levels. In vivo administration of this compound causes murine myeloma tumor cell apoptosis but does not inhibit IL-12-mediated macrophage activation and IFN-γ production by lymphocytes. Consistent with the in vitro blocking of JAK2 V617F mutant activity, treatment with this chemical at 0.5 mg/day for 10 days effectively inhibits JAK2 V617F mutant-induced tumorigenesis and tumor cell invasion in nude mice. Combined therapy with this agent and IL-12 induces greater antitumor effects than either agent alone in a murine myeloma tumor model.

Literatur
  • [4] https://pubmed.ncbi.nlm.nih.gov/10380915/
  • [5] https://pubmed.ncbi.nlm.nih.gov/11264165/
  • [6] https://pubmed.ncbi.nlm.nih.gov/12481410/
  • [7] https://pubmed.ncbi.nlm.nih.gov/16818614/
  • [8] https://pubmed.ncbi.nlm.nih.gov/19327411/

Häufig gestellte Fragen (Frequently Asked Questions)

Frage 1:
I would like to know whether it (S1143) goes to CNS through BBB, or not?

Antwort:
It can go through the BBB, as shown in this reference: http://bloodjournal.hematologylibrary.org/content/111/4/2062.full.html.