Home Protein Tyrosine Kinase EGFR inhibitor - JAK inhibitor AG-490 For research use only.

AG-490

Synonyms: Tyrphostin B42, Zinc02557947

AG-490 is an inhibitor of EGFR with IC50 of 0.1 μM in cell-free assays, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.

AG-490 Chemical Structure

AG-490 Chemical Structure

CAS No. 133550-30-8

Purity & Quality Control

AG-490 Related Products

Signaling Pathway

EGFR Signaling Pathways

EGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
Click to View More Cell Line Experimental Data

Biological Activity

Description AG-490 is an inhibitor of EGFR with IC50 of 0.1 μM in cell-free assays, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.
Targets
JAK2 (V617F) [8] EGFR [1]
(Cell-free assay)
0.1 μM
In vitro
In vitro

AG-490 inhibits HER-2 driven cell proliferation with IC50 of 3.5 μM. [1] Corresponding to the specific dose-dependent inhibition of constitutively activated JAK2 in pre-B acute leukemia (ALL) cells, AG-490 (5 μM) almost completely blocks the growth of all ALL cells by inducing programmed cell death, with no deleterious effect on normal hematopoiesis. AG-490 does not inhibit the activities of Lck, Lyn, Btk, Syk, and Src. [2] AG-490 (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. [3] AG-490 potently inhibits IL-2-mediated human T cell growth with an IC50 of 25 μM by blocking the activities of JAK3 and STAT5a/b. [4] AG-490 significantly inhibits the constitutive activation of Stat3 in MOPC, MPC11, and S194 cells, leading to dramatic dose-dependent apoptosis. [6] AG-490 (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. AG-490 (50 μM) can induce apoptosis of BaF3 cells expressing T315I and E255K mutants of Bcr-Abl. [7] AG-490 at 30 μM inhibits not only Epo-induced phosphorylation of wild-type JAK2 but also constitutive phosphorylation of the JAK2 V617F mutant. AG-490 also potently inhibits cytokine-independent cell growth induced by the JAK2 V617F mutant in BaF3 cells. [8]
Kinase Assay In vitro kinase autophosphorylation
AG-490 is dissolved in DMSO 10%-H2O-ethanol 45%. Crude membrane extracts (0.125 μg/mL) are preactivated with EGF (20 nM) in 50 mM HEPES buffer, pH 7.6, and 125 mM NaCl, for 15 minutes at 4 °C. Autophosphorylation activity of EGFR or ErbB2 kinase is assayed at 4 °C for 30 seconds in V-shaped 96-well plates. Membrane extracts (8 μL) are added to each well containing reaction mixture (12 μL, 50mM, HEPES, pH 7.4,125 mM NaCl, 12 mM M8Ac2, 2 mM MnCl2, 1 mM NaVO3, 1 μM ATP, and 1 μCi[γ-32P]ATP, final concentrations) and increasing concentrations of AG-490 (4 μL). After termination by addition of hot sample buffer, the samples are run on a 6% SDS-polyacrylamide gel electrophoresis minigel, the gels dried, and autoradiography performed during the linear exposure time period. The receptor bands are scanned densitrometrically, and the results analyzed by the Ez-Fit program. For the analysis of autophosphorylation of JAK2, JAK2 is immunoprecipitated by using anti-JAK2 antibody from lysates of G2 cells pretreated for 16 hours with increasing concentrations of AG-490 (0-50 μM). Immune complexes are then immunoblotted with anti-phosphotyrosine antibody. A dose-dependent inhibition of in vitro kinase activity is demonstrated by assessing JAK2 autophosphorylation.
Cell Research Cell lines Pre-B ALL
Concentrations Dissolved in DMSO, final concentrations ~ 50 μM
Incubation Time 16 hours
Method

Cells are exposed to different concentrations of AG-490 for 16 hours. For the determination of cell proliferation, [3H]tymidine (1 μCi) is added 6 hours or more before the cultures are terminated. Cells are then collected and samples counted in a liquid scintillation counter.
In Vivo
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. [2] In vivo administration of AG-490 causes murine myeloma tumor cell apoptosis but does not inhibit IL-12-mediated macrophage activation and IFN-γ production by lymphocytes. [6] Consistent with the in vitro blocking of JAK2 V617F mutant activity, AG-490 treatment at 0.5 mg/day for 10 days effectively inhibits JAK2 V617F mutant-induced tumorigenesis and tumor cell invasion in nude mice. [8] Combined therapy with AG-490 and IL-12 induces greater antitumor effects than either agent alone in a murine myeloma tumor model. [6]
Animal Research Animal Models SCID mice intravenously injected with ALL cells
Dosages 0.85 mg + 0.5 mg daily
Administration Continuous pump infusion supplemented with daily intraperitoneal injections
  • https://pubmed.ncbi.nlm.nih.gov/1676428/
  • https://pubmed.ncbi.nlm.nih.gov/8628398/
  • https://pubmed.ncbi.nlm.nih.gov/9192639/
  • https://pubmed.ncbi.nlm.nih.gov/10380915/
  • https://pubmed.ncbi.nlm.nih.gov/11264165/
  • https://pubmed.ncbi.nlm.nih.gov/12481410/
  • https://pubmed.ncbi.nlm.nih.gov/16818614/
  • https://pubmed.ncbi.nlm.nih.gov/19327411/

Chemical Information & Solubility

Molecular Weight 294.30 Formula

C17H14N2O3
CAS No. 133550-30-8 SDF Download AG-490 SDF
Smiles C1=CC=C(C=C1)CNC(=O)C(=CC2=CC(=C(C=C2)O)O)C#N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 58 mg/mL ( (197.07 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 9 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I would like to know whether AG490 (S1143) goes to CNS through BBB, or not?

Answer:
AG-490 can go through the BBB. You can see this reference: http://bloodjournal.hematologylibrary.org/content/111/4/2062.full.html.