Journal article
High‐Throughput Screening for Inhibitors of RGS17: A novel target for treatment of lung and prostate cancers
The FASEB journal, Vol.25, pp.802.2-802.2
04/2011
DOI: 10.1096/fasebj.25.1_supplement.802.2
Abstract
RGS17 is implicated in the growth, proliferation, metastasis and the migration of prostate and lung cancers. RGS17 is up‐regulated in lung and prostate tumor tissues by 13 fold over patient‐matched normal tissues. Reports indicate that RGS17 knockdown inhibits colony formation and decreases tumorigenesis in mice. In this study, we implemented AlphaScreen technology to develop a high‐throughput screening method for interrogating small molecule libraries for inhibitors of RGS17. Our screen utilizes a measurement of the Gα:RGS17 interaction, with an excellent Z‐score exceeding 0.73, a signal to noise ratio >70 and a screening time of 1,100 compounds per hour. We screened the NCI Diversity Set II and determined 35 initial hits and 16 were confirmed after screening against controls. The 16 compounds exhibited IC50 <10μM in dose‐response experiments for inhibiting the Gα:RGS17 interaction. Four exhibited IC50 values <6μM while inhibiting the Gα:RGS17 interaction >50% when compared to a biotinylated GST control. Immediate goals include determining the effectiveness of these compounds on inhibiting GTPase acceleration activity of RGS17 in single turnover GTPase assays and testing structurally related compounds for inhibition. This study is to establish lead compounds and develop a pharmacophore model for optimization of structure. Supported by American Cancer Society ‐ Holden Comprehensive Research Center.
Details
- Title: Subtitle
- High‐Throughput Screening for Inhibitors of RGS17: A novel target for treatment of lung and prostate cancers
- Creators
- Duncan Ian Mackie - University of IowaDavid L Roman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.25, pp.802.2-802.2
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.25.1_supplement.802.2
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- Holden Comprehensive Research Center American Cancer Society
- Language
- English
- Date published
- 04/2011
- Academic Unit
- Pharmacy; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984071947402771
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