ArticlePharmaceutical research2007
Chemogenomic analysis identifies geldanamycins as substrates and inhibitors of ABCB1.
Article in Pharmaceutical research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Article
- Calpain Genetic Disruption and HSP90 Inhibition Combine To Attenuate Mammary Tumorigenesis.Molecular and cellular biology · 2016Article
- Ascorbic acid inhibition of Candida albicans Hsp90-mediated morphogenesis occurs via the transcriptional regulator Upc2.Eukaryotic cell · 2014Article
- A novel approach for predicting P-glycoprotein (ABCB1) inhibition using molecular interaction fields.Journal of medicinal chemistry · 2011Article
- Pharmacogenomics approach reveals MRP1 (ABCC1)-mediated resistance to geldanamycins.Pharmaceutical research · 2009Article
- P-Glycoprotein-mediated resistance to Hsp90-directed therapy is eclipsed by the heat shock response.Cancer research · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeA prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting tumor growth is sufficient intracellular drug accumulation. We hypothesized that membrane transporters on tumor cells determine at least in part the response to GA analogues. MATERIALS AND
methodsTo facilitate a systematic study of chemosensitivity across a group of GA analogues with similar chemical structures, we correlated mRNA expression profiles of most known transporters with growth inhibitory potencies of compounds in 60 tumor cell lines (NCI-60). We subsequently validated the gene-drug correlations using cytotoxicity and transport assays.
resultsGeldanamycin analogues displayed a range of negative correlations coefficients with ABCB1 (MDR1, or P-glycoprotein) expression. Suppressing ABCB1 in multidrug resistant cells (NCI/ADR-RES and K562/DOX) and ABCB1-transfected cells (BC19) increased sensitivity to GA analogues, as expected for substrates. Moreover, ABCB1-mediated efflux of daunorubicin in K562/DOX cells could be blocked markedly by GA analogues in a dose-dependent fashion. The IC(50) values (half-maximum inhibition of daunorubicin efflux) were 5.5, 7.3 and 12 muM for macbecin II (NSC330500), 17-AAG (NSC330507) and GA, respectively.
conclusionsThese observations demonstrate that GA analogues are substrates as well as inhibitors of ABCB1, suggesting that drug interactions between GA analogues and other agents that are ABCB1 substrates may occur via ABCB1 in normal or tumor cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.