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Chemical Compound Review

Bosutinib     4-[(2,4-dichloro-5-methoxy- phenyl)amino]-6...

Synonyms: QCR-26, PubChem22404, SKI-606, SKI606, CHEMBL288441, ...
 
 
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Disease relevance of Bosutinib

  • These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer [1].
  • SKI-606 proved to be an active inhibitor of Bcr-Abl in several chronic myelogenous leukemia cell lines and transfectants, with IC(50) values in the low nanomolar range, 1 to 2 logs lower than those obtained with imatinib [2].
  • Analysis of lungs, liver, and spleen of these animals showed a significant decrease in GFP-positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated [3].
 

High impact information on Bosutinib

 

Biological context of Bosutinib

 

Anatomical context of Bosutinib

  • Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar [1].
  • This 4-anilino-3-quinolinecarbonitrile (SKI-606) ablates tyrosine phosphorylation of Bcr-Abl in CML cells and of v-Abl expressed in fibroblasts [5].
 

Associations of Bosutinib with other chemical compounds

 

Gene context of Bosutinib

 

Analytical, diagnostic and therapeutic context of Bosutinib

References

  1. SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Golas, J.M., Lucas, J., Etienne, C., Golas, J., Discafani, C., Sridharan, L., Boghaert, E., Arndt, K., Ye, F., Boschelli, D.H., Li, F., Titsch, C., Huselton, C., Chaudhary, I., Boschelli, F. Cancer Res. (2005) [Pubmed]
  2. In vitro and In vivo Activity of SKI-606, a Novel Src-Abl Inhibitor, against Imatinib-Resistant Bcr-Abl+ Neoplastic Cells. Puttini, M., Coluccia, A.M., Boschelli, F., Cleris, L., Marchesi, E., Donella-Deana, A., Ahmed, S., Redaelli, S., Piazza, R., Magistroni, V., Andreoni, F., Scapozza, L., Formelli, F., Gambacorti-Passerini, C. Cancer Res. (2006) [Pubmed]
  3. A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo. Jallal, H., Valentino, M.L., Chen, G., Boschelli, F., Ali, S., Rabbani, S.A. Cancer Res. (2007) [Pubmed]
  4. SKI-606 decreases growth and motility of colorectal cancer cells by preventing pp60(c-Src)-dependent tyrosine phosphorylation of beta-catenin and its nuclear signaling. Coluccia, A.M., Benati, D., Dekhil, H., De Filippo, A., Lan, C., Gambacorti-Passerini, C. Cancer Res. (2006) [Pubmed]
  5. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Golas, J.M., Arndt, K., Etienne, C., Lucas, J., Nardin, D., Gibbons, J., Frost, P., Ye, F., Boschelli, D.H., Boschelli, F. Cancer Res. (2003) [Pubmed]
  6. SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Zhang, J., Kalyankrishna, S., Wislez, M., Thilaganathan, N., Saigal, B., Wei, W., Ma, L., Wistuba, I.I., Johnson, F.M., Kurie, J.M. Am. J. Pathol. (2007) [Pubmed]
  7. 3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases. Thaimattam, R., Daga, P.R., Banerjee, R., Iqbal, J. Bioorg. Med. Chem. (2005) [Pubmed]
  8. Synthesis and Src kinase inhibitory activity of 2-phenyl- and 2-thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles. Boschelli, D.H., Wu, B., Barrios Sosa, A.C., Durutlic, H., Chen, J.J., Wang, Y., Golas, J.M., Lucas, J., Boschelli, F. J. Med. Chem. (2005) [Pubmed]
  9. Effective and selective inhibition of chronic myeloid leukemia primitive hematopoietic progenitors by the dual Src/Abl kinase inhibitor SKI-606. Konig, H., Holyoake, T.L., Bhatia, R. Blood (2008) [Pubmed]
  10. 4-Anilino-7,8-dialkoxybenzo[g]quinoline-3-carbonitriles as potent Src kinase inhibitors. Berger, D.M., Dutia, M., Birnberg, G., Powell, D., Boschelli, D.H., Wang, Y.D., Ravi, M., Yaczko, D., Golas, J., Lucas, J., Boschelli, F. J. Med. Chem. (2005) [Pubmed]
 
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