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Discovery and Development of Small Molecules That Reduce PNC Prevalence

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45




  • S. Patnaik
  • K. Frankowski
  • F. Schoenen
  • S. Huang
  • J. Norton
  • C. Wang
  • S. Titus
  • M. Ferrer
  • W. Zheng
  • N. Southall
  • V. W. Day
  • J. Aube
  • J. J. Marugan


The perinucleolar compartment (PNC) is a subnuclear body found at the periphery of the nucleolus in the nucleus. Its function is not completely known yet, but it is a highly dynamic body that is enriched with RNA transcripts and RNA-binding proteins. This compartment is highly prevalent in metastatic tumors and metastatically transformed cancer cell lines, making it a potential pan marker for metastatic progression. A high throughput, high content assay was developed to identify novel small molecules that reduce the prevalence of this metastasis biomarker in cancer cells. We have identified and further optimized a potent pyrrolopyrimidine series that reduces PNC prevalence in PC3M cells at submicromolar concentrations, where the cell viability is not affected. These compounds also show dose-dependent inhibition of migration and anchorage-independent growth in invasion and soft-agar assays, respectively. The lead candidate has drug-like physical properties and displays promising PK, making it an ideal in vivo tool for establishing the link between the PNC and the metastatic transformation of tumor cells.

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