The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

AC1MHYWA     N-(3-chlorophenyl)-6,7- dimethoxy...

Synonyms: CHEMBL540068, RTKI cpd, AG-E-19681, SureCN5477838, ANW-48170, ...
This record was replaced with 2051.
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NSC693255


High impact information on NSC693255


Chemical compound and disease context of NSC693255


Biological context of NSC693255

  • Although AG 1478 inhibited cell growth, DNA synthesis, EGFR tyrosine kinase activity, and receptor autophosphorylation of each cell line in a dose-dependent manner, it was significantly more potent in U87MG. delta EGFR cells than in the other two cell lines [2].
  • Treatment of A431 and MDA-468 human tumor cells with 0.1-10 microM AG-1478 inhibited basal and ligand-stimulated EGFR phosphorylation without a decrease in receptor content, EGF-binding sites, or binding affinity [8].
  • Receptors with a single-point mutation in the ATP binding site as well as wild-type EGFR with a covalent modification of the ATP site failed to dimerize in response to AG-1478 and AG-1517 [9].
  • Submicromolar concentrations of AG-1478 and AG-1517, quinazolines specific for inhibition of the EGFR kinase, induced reversible receptor dimerization in vitro and in intact A431 cells [9].
  • Furthermore, only the ErbB-2 inhibitor AG 879, but not the EGFR inhibitor AG 1478, abolishes androgen-induced cell proliferation [10].

Anatomical context of NSC693255

  • The EGFR ligands EGF (100 ng ml(-1)), transforming growth factor alpha (0.4 ng ml(-1)) and heparin-binding EGF (100 ng ml(-1)) all caused a 20% increase in maxi-K(Ca) channel current that was blocked by AG-1478 or by knock-down of EGFR expression using cisterna magna infusion of antisense oligodeoxynucleotide (AS-ODN) [11].
  • AG-1478 also inhibited goblet cell secretion [12].
  • Identification of downstream molecular targets for AG-1478, in marrow stromal cells, might prove useful in designing more selective drugs, capable of separating proliferative from differentiation-inducing activities [4].
  • Previous reports have shown that genistein and tyrphostin AG-1478, two tyrosine kinase inhibitors (TKIs), exert multiple cellular effects in prostate carcinoma cells, e.g. a reduction in the production of urokinase plasminogen activator (uPA) and its receptor uPAR, and a decrease in the cells' ability to invade an artificial basement membrane [13].

Associations of NSC693255 with other chemical compounds


Gene context of NSC693255

  • This effect was inhibited by treatment with a selective inhibitor of EGFR phosphorylation (AG 1478) and by an EGFR neutralizing Ab [18].
  • The expression of c-Myc and of Sp1 proteins, transcription factors for hTERT, were also suppressed by AG 1478 in HSC-1 cells, but the expression of Ets-2 protein, another transcription factor, was not affected [19].
  • Reoxygenation following 4-h hypoxia-stimulated cell proliferation, which was dependent on ERK and Akt activation and was also inhibited by antioxidants and AG 1478 [20].
  • In response to ET-1, ERK1/2 phosphorylation was increased by 27 +/- 1-fold and attenuated by AG-1478, a specific EGF-R inhibitor, to 9 +/- 1-fold [21].
  • Activation of ERK1/2 and its interaction with caveolin-1 were reduced by AG-1478, beta-cyclodextrin, or inhibition of PKC [21].

Analytical, diagnostic and therapeutic context of NSC693255


  1. Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice. Lenferink, A.E., Simpson, J.F., Shawver, L.K., Coffey, R.J., Forbes, J.T., Arteaga, C.L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors. Han, Y., Caday, C.G., Nanda, A., Cavenee, W.K., Huang, H.J. Cancer Res. (1996) [Pubmed]
  3. Cyclic stretch activates ERK1/2 via G proteins and EGFR in alveolar epithelial cells. Correa-Meyer, E., Pesce, L., Guerrero, C., Sznajder, J.I. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  4. Opposing effects of tyrosine kinase inhibitors on mineralization of normal and tumor bone cells. Klein, B.Y., Tepper, S.H., Gal, I., Shlomai, Z., Ben-Bassat, H. J. Cell. Biochem. (1997) [Pubmed]
  5. Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival. Wang, Y., Pennock, S., Chen, X., Wang, Z. Mol. Cell. Biol. (2002) [Pubmed]
  6. Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent kinase 2 activation induce growth arrest, differentiation, and apoptosis of human papilloma virus 16-immortalized human keratinocytes. Ben-Bassat, H., Rosenbaum-Mitrani, S., Hartzstark, Z., Shlomai, Z., Kleinberger-Doron, N., Gazit, A., Plowman, G., Levitzki, R., Tsvieli, R., Levitzki, A. Cancer Res. (1997) [Pubmed]
  7. Tyrosine kinase inhibitors alter adhesivity of prostatic cancer cells to extracellular matrix components. Skogseth, H., Holt, R.U., Larsson, E., Halgunset, J. APMIS (2006) [Pubmed]
  8. Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent of MAPK activity. Busse, D., Doughty, R.S., Ramsey, T.T., Russell, W.E., Price, J.O., Flanagan, W.M., Shawver, L.K., Arteaga, C.L. J. Biol. Chem. (2000) [Pubmed]
  9. Unliganded epidermal growth factor receptor dimerization induced by direct interaction of quinazolines with the ATP binding site. Arteaga, C.L., Ramsey, T.T., Shawver, L.K., Guyer, C.A. J. Biol. Chem. (1997) [Pubmed]
  10. Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells. Meng, T.C., Lee, M.S., Lin, M.F. Oncogene (2000) [Pubmed]
  11. Adenylate cyclase 5 and KCa1.1 channel are required for EGFR up-regulation of PCNA in native contractile rat basilar artery smooth muscle. Ivanov, A., Gerzanich, V., Ivanova, S., Denhaese, R., Tsymbalyuk, O., Simard, J.M. J. Physiol. (Lond.) (2006) [Pubmed]
  12. Cholinergic agonists transactivate EGFR and stimulate MAPK to induce goblet cell secretion. Kanno, H., Horikawa, Y., Hodges, R.R., Zoukhri, D., Shatos, M.A., Rios, J.D., Dartt, D.A. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  13. Transcription levels of invasion-related genes in prostate cancer cells are modified by inhibitors of tyrosine kinase. Skogseth, H., Follestad, T., Larsson, E., Halgunset, J. APMIS (2006) [Pubmed]
  14. Epidermal growth factor induces p11 gene and protein expression and down-regulates calcium ionophore-induced arachidonic acid release in human epithelial cells. Huang, X.L., Pawliczak, R., Cowan, M.J., Gladwin, M.T., Madara, P., Logun, C., Shelhamer, J.H. J. Biol. Chem. (2002) [Pubmed]
  15. Antagonistic and agonistic effects of quinazoline tyrosine kinase inhibitors on mutant EGF receptor function. Montgomery, R.B. Int. J. Cancer (2002) [Pubmed]
  16. Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor. Iwasaki, H., Eguchi, S., Ueno, H., Marumo, F., Hirata, Y. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  17. PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation. Mendez, M., LaPointe, M.C. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  18. Pseudomonas Lipopolysaccharide Accelerates Wound Repair via Activation of a Novel Epithelial Cell Signaling Cascade. Koff, J.L., Shao, M.X., Kim, S., Ueki, I.F., Nadel, J.A. J. Immunol. (2006) [Pubmed]
  19. Inhibition of the epidermal growth factor receptor suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma cells. Budiyanto, A., Bito, T., Kunisada, M., Ashida, M., Ichihashi, M., Ueda, M. J. Invest. Dermatol. (2003) [Pubmed]
  20. Signal transduction of MEK/ERK and PI3K/Akt activation by hypoxia/reoxygenation in renal epithelial cells. Kwon, D.S., Kwon, C.H., Kim, J.H., Woo, J.S., Jung, J.S., Kim, Y.K. Eur. J. Cell Biol. (2006) [Pubmed]
  21. Endothelin-1 activates mesangial cell ERK1/2 via EGF-receptor transactivation and caveolin-1 interaction. Hua, H., Munk, S., Whiteside, C.I. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  22. Preclinical analysis of the analinoquinazoline AG1478, a specific small molecule inhibitor of EGF receptor tyrosine kinase. Ellis, A.G., Doherty, M.M., Walker, F., Weinstock, J., Nerrie, M., Vitali, A., Murphy, R., Johns, T.G., Scott, A.M., Levitzki, A., McLachlan, G., Webster, L.K., Burgess, A.W., Nice, E.C. Biochem. Pharmacol. (2006) [Pubmed]
  23. Direct inhibition of the cloned Kv1.5 channel by AG-1478, a tyrosine kinase inhibitor. Choi, B.H., Choi, J.S., Rhie, D.J., Yoon, S.H., Min, d.o. .S., Jo, Y.H., Kim, M.S., Hahn, S.J. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  24. Preferential inhibition of glioblastoma cells with wild-type epidermal growth factor receptors by a novel tyrosine kinase inhibitor ethyl-2,5-dihydroxycinnamate. Han, Y., Caday, C.G., Umezawa, K., Nanda, A. Oncol. Res. (1997) [Pubmed]
WikiGenes - Universities