Home Protein Tyrosine Kinase EGFR inhibitor AG-1478

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AG-1478 EGFR inhibitor

Cat.No.S2728

AG-1478 is a selective EGFR inhibitor with IC50 of 3 nM in cell-free assays, almost no activity on HER2-Neu, PDGFR, Trk, Bcr-Abl and InsR. This compound inhibits encephalomyocarditis virus (EMCV) and hepatitis c virus (HCV) by targeting phosphatidylinositol 4-kinase IIIα (PI4KA).
AG-1478 EGFR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 315.75

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Quality Control

Batch: S272801 DMSO]25 mg/mL]false]Ethanol]13 mg/mL]false]Water]Insoluble]false Purity: 99.92%
  • Cited in Nature Medicine for its top-tier quality
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  • NMR
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99.92

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U87MG Growth inhibitory assay ~100 μM DMSO IC50=34.6 μM 8752145
U87MG.ΔEGFR Growth inhibitory assay ~100 μM DMSO IC50=8.7 μM 8752145
U87MG.wtEGFR. Growth inhibitory assay ~100 μM DMSO IC50=48.4 μM 8752145
U87MG Kinase assay ~100 μM DMSO inhibits EGFR tyrosine kinase activity 8752145
U87MG.ΔEGFR Kinase assay ~100 μM DMSO inhibits EGFR tyrosine kinase activity 8752145
U87MG.wtEGFR. Kinase assay ~100 μM DMSO inhibits EGFR tyrosine kinase activity 8752145
HPV 16-immortalized human keratinocytes Growth inhibitory assay ~50 μM DMSO inhibits cell growth 9288782
HPV 16-immortalized human keratinocytes Function assay ~50 μM DMSO induces arrest in the Cell Cycle 9288782
HPV 16-immortalized human keratinocytes Apoptosis assay ~50 μM DMSO induces apoptosis. 9288782
A431 Kinase assay ~10 μM DMSO inhibits the basal and TGF-α-stimulated tyrosine phosphorylation of the EGFR 10702262
MDA-468  Kinase assay ~10 μM DMSO inhibits the basal and TGF-α-stimulated tyrosine phosphorylation of the EGFR 10702262
A431 Function assay ~10 μM DMSO induces cell cycle arrest 10702262
MDA-MB-231 Kinase assay ~5 μM DMSO inhibits EGF stimulated phosphorylation of FKHR 11030146
CNE2 Growth inhibitory assay 100 μM DMSO inhibits cell proliferation by 98.4% 11410322
CNE2 Kinase assay ~100 μM DMSO inhibits EGFR tyrosine phosphorylation 11410322
CNE2 Function assay ~100 μM DMSO Inhibits MAPK and AKT activation 11410322
CNE2 Function assay ~50 μM DMSO affects cell cycle distribution 11410322
HSC-2 Kinase assay 8 μM DMSO inhibits phosphorylation of EGFR and Akt 17689285
HSC-2 Apoptosis assay 8 μM DMSO inhibits Fas-mediated apoptosis 17689285
HEp-2 Growth inhibitory assay ~10 μM DMSO enhances oridonin-induced growth-inhibitory 20202741
SubG1 Apoptosis assay ~10 μM DMSO enhances oridonin-induced apoptosis 20202741
HEp-2 Function assay ~10 μM DMSO enhances Oridonin-induced Bax activation, Bcl-2 degradation and SIRT1 inactivation 20202741
H508 Growth inhibitory assay ~1 μM DMSO mitigates CPF-mediated H508 cell growth 26514924
A431 Antiproliferative assay Tested for antiproliferative activity against human A431 cells, IC50=20μM 15109642
HeLa Function assay 30 mins Inhibition of EGFR autophosphorylation in human HeLa cells preincubated for 30 mins prior to EGF stimulation by Western blotting 21718029
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
HEK293 Function assay 1 hr Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, Ki=1.87μM 29941193
HEK293 Function assay 1 hr Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, IC50=19.6μM 29941193
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Solubility

In vitro
Batch:

DMSO : 25 mg/mL (79.17 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 13 mg/mL

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 315.75 Formula

C16H14ClN3O2

 Storage (From the date of receipt)
CAS No. 153436-53-4,175178-82-2 Download SDF Storage of Stock Solutions

Synonyms Tyrphostin AG-1478, NSC 693255 Smiles COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)Cl)OC

Mechanism of Action

Targets/IC50/Ki
EGFR
(Cell-free assay)
3 nM
In vitro

AG-1478 is high selective over ErbB2 and PDGFR with IC50 of >100 μM. This compound preferentially inhibits U87MG cells expressing truncated EGFR with IC50 of 8.7 μM, compared to those expressing endogenous wt EGFR or overexpressing exogenous wt EGFR with IC50 of 34.6 μM and 48.4 μM, respectively, and inhibits the DNA synthesis with IC50 of 4.6 μM, 19.67 μM, and 35.2 μM, respectively. This chemical also preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR compared to endogenous or overexpressed exogenous wt EGFR. It (0.25 μM) abolishes the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. This compound inhibits EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells with IC50 of 0.07 μM and 0.2 μM, respectively. It is able to inhibit the function of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2, with a more pronounced effect on ABCG2.

In vivo

Administration of AG-1478 blocks phosphorylation of the EGFR at the tumor site and inhibits the growth of A431 xenografts that overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR. Even subtherapeutic doses of this compound significantly enhance the efficacy of cytotoxic drugs, with the combination of this chemical displaying synergistic antitumor activity against human glioma xenografts. The combination of this compound and an anti-EGFR antibody (mAb 806) displays additive and in some cases synergistic, antitumor activity against tumor xenografts overexpressing the EGFR. The combination of this compound (0.4 mg) with a single dose of 25 μCi 90Y-CHX-A''-DTPA-hu3S193 results in a significant enhancement of efficacy compared with either agent alone.

References
  • [4] https://pubmed.ncbi.nlm.nih.gov/14676326/
  • [5] https://pubmed.ncbi.nlm.nih.gov/16203806/
  • [6] https://pubmed.ncbi.nlm.nih.gov/16522318/
  • [7] https://pubmed.ncbi.nlm.nih.gov/19059384/
  • [8] https://pubmed.ncbi.nlm.nih.gov/19148526/
  • [9] https://pubmed.ncbi.nlm.nih.gov/21472266/

Applications

Methods Biomarkers Images PMID
Growth inhibition assay Cell viability
S2728-viability1
25258648
Western blot Shc / PLC-γ1 EGFR / Neu / p-Tyr
S2728-WB2
10931950

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