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AG-490

AG-490 (Tyrphostin B42) is an inhibitor of EGFR, ErbB2 and JAK2 with IC50 of 0.1 μM, 13.5 μM, and ~10 μM, respectively.

Catalog No.S1143

: Tel: +1-832-582-8158[email protected]

AG-490 Chemical Structure
Molecular Weight: 294.30

Validation & Quality Control

Product Citations(2)

Prostate, 2012, ahead of print

Biochem Biophys Res Commun, 2013, 429(3-4), 156-162

Quality Control & MSDS

Related Compound Libraries

AG-490 is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) Tyrosine Kinase Inhibitor Library (96-Well)

Product Information

Compare EGFR Inhibitors

Research Area
Research Area
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1023	Erlotinib HCl	<1 mg/mL	3 mg/mL	<1 mg/mL
S1025	Gefitinib (Iressa)	<1 mg/mL	89 mg/mL	4 mg/mL
S1028	Lapatinib Ditosylate (Tykerb)	<1 mg/mL	185 mg/mL	<1 mg/mL
S1011	Afatinib (BIBW2992)	<1 mg/mL	97 mg/mL	15 mg/mL
S1143	AG-490	<1 mg/mL	59 mg/mL	6 mg/mL
S2111	Lapatinib	<1 mg/mL	100 mg/mL	<1 mg/mL
S1167	CP-724714	<1 mg/mL	94 mg/mL	94 mg/mL
S2727	Dacomitinib (PF299804,PF-00299804)	<1 mg/mL	19 mg/mL	<1 mg/mL
S2728	AG-1478 (Tyrphostin AG-1478)	<1 mg/mL	25 mg/mL	13 mg/mL
S1019	CI-1033 (Canertinib)	<1 mg/mL	2 mg/mL	9 mg/mL
S1194	CUDC-101	<1 mg/mL	20 mg/mL	<1 mg/mL
S2150	Neratinib (HKI-272)	<1 mg/mL	2 mg/mL	<1 mg/mL
S1173	WZ4002	<1 mg/mL	13 mg/mL	<1 mg/mL
S1392	Pelitinib (EKB-569)	<1 mg/mL	13 mg/mL	<1 mg/mL
S2192	AZD8931	<1 mg/mL	40 mg/mL	<1 mg/mL
S2185	AST-1306	<1 mg/mL	124 mg/mL	<1 mg/mL
S2752	Arry-380	<1 mg/mL	114 mg/mL	<1 mg/mL
S1079	PD153035 HCl	<1 mg/mL	0.5 mg/mL	<1 mg/mL
S2755	ARRY334543	<1 mg/mL	6 mg/mL	<1 mg/mL
S2867	WHI-P154	<1 mg/mL	75 mg/mL	<1 mg/mL
S1179	WZ8040	<1 mg/mL	96 mg/mL	3 mg/mL
S2205	OSI-420	2 mg/mL	83 mg/mL	<1 mg/mL
S1056	BMS-599626 (AC480)	<1 mg/mL	113 mg/mL	20 mg/mL
S1486	AEE788 (NVP-AEE788)	<1 mg/mL	88 mg/mL	<1 mg/mL
S2784	TAK-285	<1 mg/mL	110 mg/mL	54 mg/mL
S2826	Desmethyl Erlotinib (CP-473420)	<1 mg/mL	11 mg/mL	5 mg/mL
S8009	AG 18 (Tyrphostin 23)	<1 mg/mL	37 mg/mL	37 mg/mL
S1170	WZ3146	<1 mg/mL	93 mg/mL	<1 mg/mL
S2895	Tyrphostin 9 (SF 6847)	<1 mg/mL	56 mg/mL	56 mg/mL
S2922	Icotinib	<1 mg/mL	78 mg/mL	7 mg/mL
S7039	PD168393	<1 mg/mL	74 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Product Citations Tech Support & FAQs

Biological Activity

Description	AG-490 (Tyrphostin B42) is an inhibitor of EGFR, ErbB2 and JAK2 with IC50 of 0.1 μM, 13.5 μM, and ~10 μM, respectively.
Targets	EGFR	ErbB2	JAK2
IC50	0.1 μM	13.5 μM ^[1]	~10 μM ^[2]
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] Although AG-490 alone has no effect on proliferation of FDrv210H cells at a concentration of 5 μM, AG-490 can synergize with STI571 to enhance its inhibitory effect on p210^bcr-abl driven proliferation. ^[5] 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 imatinib-resistant 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]
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]
Clinical Trials
Features

Protocol(Only for Reference)

Kinase Assay:
^[1]

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.

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 Assay:
^[2]

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.

Animal Study:
^[2]

Animal Models	SCID mice intravenously injected with ALL cells
Formulation	Dissolved in DMSO
Dosages	0.85 mg + 0.5 mg daily
Administration	Continuous pump infusion supplemented with daily intraperitoneal injections

References

Chemical Information

Download AG-490 SDF

Molecular Weight (MW)	294.30
Formula	C₁₇H₁₄N₂O₃
CAS No.	133550-30-8
Synonyms	N/A

Solubility (25°C) DMSO 59 mg/mL Water <1 mg/mL Ethanol 6 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	(E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Product Citations (2)

The Activity of the Androgen Receptor Variant AR-V7 Is Regulated by FOXO1 in a PTEN-PI3K-AKT-Dependent Way [Sanjay N, et al. Prostate 2012;ahead of print]
PubMed: 22821817
RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis. [Li C, et al. Biochem Biophys Res Commun 2013;429(3-4), 156-162]
PubMed: 23142594

Tech Support & FAQs

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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AG-490