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Series GSE94783 Query DataSets for GSE94783
Status Public on Mar 06, 2017
Title A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Approved drugs are invaluable tools to study biochemical pathways and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here, we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered the synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these two drugs modulates the stability of the androgen receptor (AR) and resensitizes AR mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for γ-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC might be repurposed to tackle resistance to antiandrogens in prostate cancer patients.
Overall design Two biological replicates were produced for each condition. Drug treatment was compared to vehicle-treated cells.
Contributor(s) Licciardello MP, Ringler A, Markt P, Klepsch F, Lardeau C, Sdelci S, Schirghuber E, Müller AC, Caldera M, Wagner A, Herzog R, Penz T, Schuster M, Boidol B, Dürnberger G, Folkvaljon Y, Stattin P, Ivanov V, Colinge J, Bock C, Kratochwill K, Menche J, Bennett KL, Kubicek S
Citation(s) 28530711
Submission date Feb 10, 2017
Last update date May 15, 2019
Contact name Marco Paolo Licciardello
Organization name The Institute of Cancer Research
Street address 15 Cotswold Road
City London
ZIP/Postal code SM2 5NG
Country United Kingdom
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (8)
GSM2482834 DMSO_1
GSM2482835 DMSO_2
GSM2482836 Flutamide_1
BioProject PRJNA374038
SRA SRP099217

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Supplementary file Size Download File type/resource
GSE94783_rnaseq_process_cuffdiff_global_DMSO_Flut_PPC_genes_diff.tsv.gz 3.0 Mb (ftp)(http) TSV
GSE94783_rnaseq_process_cuffdiff_global_DMSO_Flut_genes_diff.tsv.gz 3.0 Mb (ftp)(http) TSV
GSE94783_rnaseq_process_cuffdiff_global_DMSO_PPC_genes_diff.tsv.gz 3.0 Mb (ftp)(http) TSV
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