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Updated: May 4, 2026
High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
Development and validation of high-throughput screening assays for poly(ADP-ribose) polymerase-2 inhibitors
Zhixiang Zhu1, Jing Jin1, Nina Xue1
1Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
Abstract:
Poly(ADP-ribose) polymerase-1 and -2 (PARP1/2) are two key facilitators of DNA repair and are implicated in the pathogenesis of cancers and several chronic diseases. Inhibitors of PARP1/2 have shown powerful therapeutic effects in the treatment of cancer, cerebral ischemia, and inflammation. In addition, evidence from several studies suggests unique functions for PARP2 in genome surveillance, spermatogenesis, adipogenesis, and T cell development, and PARP2-specific inhibitors might have many other applications. To acquire PARP1/2 inhibitors, many high-throughput screening (HTS) assays for PARP1 inhibitors have been developed. However, detailed screening assays for PARP2 inhibitors have not been reported. Herein, three HTS assays for PARP2 inhibitors were developed and validated with reference inhibitors in each case. The results suggest that the HTS assays for PARP2 inhibitors using chemical quantification of NAD(+), biotin-based quantification of PAR, and ELISA quantification of PAR are sensitive, robust, and cost effective.
Insights
New high-throughput screening (HTS) assays for Poly(ADP-ribose) polymerase-2 (PARP2) inhibitors were developed. These sensitive, robust, and cost-effective assays enable the discovery of novel PARP2-specific therapeutics for various diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Poly(ADP-ribose) polymerase-1 and -2 (PARP1/2) are crucial for DNA repair and implicated in cancer and chronic diseases.
- PARP1/2 inhibitors show therapeutic potential in cancer, ischemia, and inflammation.
- PARP2 has unique roles in genome surveillance, reproduction, and immunity, suggesting applications for PARP2-specific inhibitors.
Purpose of the Study:
- To develop and validate high-throughput screening (HTS) assays specifically for Poly(ADP-ribose) polymerase-2 (PARP2) inhibitors.
- To address the lack of reported detailed screening assays for PARP2 inhibitors.
Main Methods:
- Development of three distinct HTS assays for PARP2 inhibition.
- Assays utilized chemical quantification of NAD(+), biotin-based quantification of PAR, and ELISA quantification of PAR.
- Validation of assays using reference inhibitors.
Main Results:
- Successful development and validation of three novel HTS assays for PARP2 inhibitors.
- The developed assays demonstrated sensitivity, robustness, and cost-effectiveness.
- These assays provide a foundation for identifying PARP2-specific drug candidates.
Conclusions:
- The newly developed HTS assays are suitable for screening and identifying PARP2 inhibitors.
- These assays will facilitate the discovery of novel therapeutics targeting PARP2.
- The findings support the potential of PARP2-specific inhibitors in various therapeutic areas.
