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Title: "Drug-seq": An Approach to Identify the Genomic Targets of Chemicals Identified by Functional Phenotypic Screens [Drug-seq]      
keywords:
Epigenomics
ID:
PRJNA241278
description:
Here we report an approach that has permitted us to uncover the sites and mechanisms of action of a drug, referred to as SD70, initially identified by phenotypic screening for inhibitors of ligand and genotoxic stress-induced translocations in prostate cancer cells. Based on synthesis of a derivatized form of SD70 that permits its application for a ChIP-seq-like approach, referred to as Drug-seq, we were next able to efficiently map the genome-wide binding locations of this small molecule, revealing that it largely co-localized with androgen receptor (AR) on regulatory enhancers. Based on these observations, we performed the appropriate global analyses to ascertain that SD70 inhibits the androgen-dependent AR program, and prostate cancer cell growth, acting, at least in part, by functionally inhibiting the jumonji (JMJ) domain-containing demethylase, KDM4C. Drug-seq represents a powerful strategy for new drug development by mapping genome-wide location of small molecules, a powerful adjunct to contemporary drug development strategies. Overall design: Drug-seq assay followed by high-throughput sequencing (HT-seq).
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA241278
authentication:
none
authorization:
none
ID:
pmid:24928520
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • K99 DK094981/DK/NIDDK NIH HHS/United States

  • 1K99DK094981-01/DK/NIDDK NIH HHS/United States

  • R01 NS034934/NS/NINDS NIH HHS/United States

  • R01 CA173903/CA/NCI NIH HHS/United States

  • PC111467/PC/NCI NIH HHS/United States

  • 4R00CA166527-02/CA/NCI NIH HHS/United States

  • R37 DK039949/DK/NIDDK NIH HHS/United States

  • DK18477/DK/NIDDK NIH HHS/United States

  • R00 CA166527/CA/NCI NIH HHS/United States

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