ipi-493 and Breast-Neoplasms

ipi-493 has been researched along with Breast-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for ipi-493 and Breast-Neoplasms

ArticleYear
Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives.
    Journal of medicinal chemistry, 1995, Sep-15, Volume: 38, Issue:19

    The erbB-2 oncogene encodes a transmembrane protein tyrosine kinase which plays a pivotal role in signal transduction and has been implicated when overexpressed in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the quinoid moiety of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2 (FRE/erbB-2). Specifically, dosed intraperitoneally at 100 mg/kg, 17-(allylamino)-17-demethoxygeldanamycin and other 17-amino analogs were effective at reducing p185 phosphotyrosine in subcutaneous flank FRE/erbB-2 tumors. Modifications to the 17-19-positions of the quinone ring revealed a broad structure-activity relationship in vitro.

    Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzoquinones; Breast Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Lactams, Macrocyclic; Mice; Mice, Nude; Phosphotyrosine; Protein-Tyrosine Kinases; Quinones; Rats; Receptor, ErbB-2; Rifabutin; Structure-Activity Relationship; Transfection; Tumor Cells, Cultured

1995
erbB-2 oncogene inhibition by geldanamycin derivatives: synthesis, mechanism of action, and structure-activity relationships.
    Journal of medicinal chemistry, 1995, Sep-15, Volume: 38, Issue:19

    Overexpression of the erbB-2 oncogene has been linked to poor prognosis in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the ansa ring of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2. Functional group modification in the ansa ring was performed stereoselectively and regiospecifically without the need for protection strategies. Essential functional groups that were required for anti-erbB-2 activity were the 7-carbamate and the 2,3-double bond. Modification of the functional groups at the other positions was permitted. Structure-activity relationships are described for 1-5-, 7-9-, 11-, 15-, and 22-substituted geldanamycins.

    Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzoquinones; Breast Neoplasms; Female; Genes, erbB-2; Humans; Lactams, Macrocyclic; Mice; Mice, Nude; Molecular Conformation; Molecular Structure; Protein-Tyrosine Kinases; Quinones; Rats; Receptor, ErbB-2; Structure-Activity Relationship; Transfection

1995
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