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novobiocin/cáncer de mama
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Using novobiocin as a specific inhibitor of breast cancer resistant protein to assess the role of transporter in the absorption and disposition of topotecan.
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OBJECTIVE
To investigate the role of intestinal breast cancer resistant protein (BCRP) in the absorption and disposition of topotecan (TPT) using novobiocin (NOV) as a specific inhibitor.
METHODS
Transporter inhibition specificity of NOV was assessed in cells overexpressing BCRP or Pgp.
Novobiocin in combination with high-dose chemotherapy for the treatment of advanced breast cancer: a phase 2 study.
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We conducted the first phase 2 and pharmacologic study to evaluate the combination of novobiocin (a coumeromycin antibiotic that has been shown to augment alkylating agent cytotoxicity in experimental models) and high-dose cyclophosphamide and thiotepa followed by autologous marrow support in women
Usefulness of novobiocin as a selective inhibitor of intestinal breast cancer resistance protein (Bcrp) in rats.
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1. We investigated whether novobiocin is useful for elucidating the contribution of breast cancer resistance protein (Bcrp) to intestinal absorption without affecting the activities of P-glycoprotein (P-gp), cytochrome P450 (CYP) 3A and hepatic organic anion transporting polypeptide (Oatp) in
Novobiocin decreases SMYD3 expression and inhibits the migration of MDA-MB-231 human breast cancer cells.
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SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase that plays an important role in transcriptional regulation in human carcinogenesis, and heat-shock protein HSP90A has been shown to increase the activity of SMYD3. We previously reported that overexpression of SMYD3
Phase I and pharmacologic study of the alkylating agent modulator novobiocin in combination with high-dose chemotherapy for the treatment of metastatic breast cancer.
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OBJECTIVE
Resistance to alkylators may potentially be overcome by drugs that inhibits DNA repair, thus improving the efficacy of high-dose chemotherapy. This trial was performed to determine if novobiocin, an agent that inhibits DNA repair, could be given with high-dose alkylators. Study aims were
Antitumor activity of nanoliposomes encapsulating the novobiocin analog 6BrCaQ in a triple-negative breast cancer model in mice.
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In this study, we investigated the anticancer efficacy of pegylated liposomes containing 6BrCaQ, an hsp90 inhibitor derived from novobiocin. 6BrCaQ has been previously identified as the most potent compound in a series of quinoleic novobiocin analogs but is poorly water-soluble. We investigated, for
New novobiocin analogues as antiproliferative agents in breast cancer cells and potential inhibitors of heat shock protein 90.
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Selective hsp90 inhibitors simultaneously destabilize and deplete key signaling proteins involved in cell proliferation and survival, angiogenesis, and metastasis. Investigation of novobiocin analogues lacking the noviose moiety as novel inhibitors of hsp90 was carried out. A novel series of
Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic.
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Breast cancer resistance protein (BCRP/ABCG2) of an ATP-binding cassette half-transporter confers resistance against mitoxantrone and camptothecin derivatives of topotecan and irinotecan. Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro
Modulation of breast cancer resistance protein (BCRP/ABCG2) gene expression using RNA interference.
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Overexpression of the breast cancer resistance protein (BCRP/ABCG2) confers multidrug resistance (MDR) to tumor cells and often limits the efficacy of chemotherapy. To circumvent BCRP-mediated MDR, a common approach is the use of potent and specific inhibitors of BCRP transport such as fumitremorgin
Insulin suppresses the expression and function of breast cancer resistance protein in primary cultures of rat brain microvessel endothelial cells.
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The aim of this study was to investigate the role of insulin in the regulation of breast cancer resistance protein (BCRP) function and expression using primary cultured rat brain microvessel endothelial cells (rBMECs) as an in vitro model of the blood brain barrier (BBB). The prazosin uptake assay
Validation of membrane vesicle-based breast cancer resistance protein and multidrug resistance protein 2 assays to assess drug transport and the potential for drug-drug interaction to support regulatory submissions.
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Breast cancer resistance protein (BCRP) and multidrug resistance protein 2 (MRP2) can play a role in the absorption, distribution, metabolism, and excretion of drugs, impacting on the potential for drug-drug interactions. This study has characterized insect cell- and mammalian cell-derived
Novobiocin is a potent inhibitor for human organic anion transporters.
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Organic anion transporters (OATs) mediate the body disposition of a diverse array of environmental toxins and clinically important drugs. Previous studies have shown that novobiocin, an inhibitor for breast cancer resistance proteins (BCRP), inhibited organic anion transport. However, its
3D-QSAR Assisted Design, Synthesis and Evaluation of Novobiocin Analogues.
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Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure-activity relationships. Based upon the most potent
Synthesis and biological evaluation of arylated novobiocin analogs as Hsp90 inhibitors.
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Novobiocin analogs lacking labile glycosidic ether have been designed, synthesized and evaluated for Hsp90 inhibitory activity. Replacement of the synthetically complex noviose sugar with simple aromatic side chains produced analogs that maintain moderate cytotoxic activity against MCF7 and SkBR3
Novobiocin analogues with second-generation noviose surrogates.
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Hsp90 is a promising therapeutic target for the treatment of cancer. Novobiocin is the first Hsp90 C-terminal inhibitor ever identified and recent structure-activity relationship studies on the noviose sugar identified several commercially available amines as suitable surrogates. In an effort to
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