October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Poster Sessions
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Research Festival Committees
- Past Research Festivals
2011 program
Download the 2011 Research Festival Program Book
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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 |
NCATS |
CANCER-25 |
Authors
- 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
Abstract
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.
