MPC309 Modulates Androgen Receptor Transcriptional Activity to Inhibit Therapy-Resistant Prostate Cancer
- Description
Prostate cancer cells depend on the androgen receptor (AR) for survival and proliferation. This study examined the antitumor effects of compound MPC309, a trivalent display of ethisterone conjugated to a peptoid oligomer backbone that binds to the AR with nanomolar affinity. First, a structure-activity relationship study was performed to improve multivalent peptoid conjugate potency. Then, the impact of MPC309 on AR-mediated gene expression, AR occupancy, chromatin accessibility, and AR’s interaction with coregulatory proteins was examined. The dataset includes sequencing data, which contains ChIP sequencing, ATAC sequencing, and RNA sequencing data. For sequencing experiments, LNCaP-abl cells were cultured under androgen deprivation and treated with:
- ChIP-seq: vehicle (DMSO), 1μM backbone, 1μM MPC309, 10nM DHT, or 10μM enzalutamide overnight
- ATAC-seq: vehicle (DMSO), 1μM backbone, 1μM MPC309, 10nM DHT, or 10μM enzalutamide overnight
- RNA-seq: vehicle (DMSO), 1μM peptoid backbone lacking the ethisterone moieties, 1μM MPC309, 10nM DHT, or 10μM enzalutamide overnight; vehicle (DMSO), 1μM MPC309, or 10μM ethisterone overnight
Access
- Restrictions
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Free to All
- Instructions
- The datasets generated and analyzed during the current study are available in the Gene Expression Omnibus (GEO) repository.
- Grant Support
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Prostate and Testicular Cancer Research and Education Fund/New York State Department of Health2002890/NSFMD/PhD Vilcek Scholars/NYU Langone Health