{"title":"PARP抑制剂靶区和脱靶区分析方法","authors":"Daniel S. Bejan, Michael S. Cohen","doi":"10.1016/j.crchbi.2022.100027","DOIUrl":null,"url":null,"abstract":"<div><p>PARP inhibitor development is on the rise as more PARP family members emerge as novel drug targets in diseases such as cancer, inflammation, and viral infection. Understanding a drug's mechanism of action and potential risks for toxicity requires proteome-wide characterization of both on- and off-target engagement. This review will highlight different methods to map out the protein interaction profile of a small molecule, using the clinically approved PARP inhibitors as a case study. The approaches discussed here will mainly focus on chemoproteomic workflows, using inhibitor bead-conjugates and photoaffinity labeling probes, but will also touch on the utility of biochemical assays. Collectively, these strategies have revealed new targets for PARP inhibitors beyond the expected PARP1/2, providing valuable insights for understanding mechanism of action, toxicity, and polypharmacology.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"2 ","pages":"Article 100027"},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266624692200009X/pdfft?md5=eef9a42217a59c9adbae10a8602b14e0&pid=1-s2.0-S266624692200009X-main.pdf","citationCount":"2","resultStr":"{\"title\":\"Methods for profiling the target and off-target landscape of PARP inhibitors\",\"authors\":\"Daniel S. Bejan, Michael S. Cohen\",\"doi\":\"10.1016/j.crchbi.2022.100027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>PARP inhibitor development is on the rise as more PARP family members emerge as novel drug targets in diseases such as cancer, inflammation, and viral infection. Understanding a drug's mechanism of action and potential risks for toxicity requires proteome-wide characterization of both on- and off-target engagement. This review will highlight different methods to map out the protein interaction profile of a small molecule, using the clinically approved PARP inhibitors as a case study. The approaches discussed here will mainly focus on chemoproteomic workflows, using inhibitor bead-conjugates and photoaffinity labeling probes, but will also touch on the utility of biochemical assays. Collectively, these strategies have revealed new targets for PARP inhibitors beyond the expected PARP1/2, providing valuable insights for understanding mechanism of action, toxicity, and polypharmacology.</p></div>\",\"PeriodicalId\":72747,\"journal\":{\"name\":\"Current research in chemical biology\",\"volume\":\"2 \",\"pages\":\"Article 100027\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S266624692200009X/pdfft?md5=eef9a42217a59c9adbae10a8602b14e0&pid=1-s2.0-S266624692200009X-main.pdf\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current research in chemical biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S266624692200009X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current research in chemical biology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266624692200009X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Methods for profiling the target and off-target landscape of PARP inhibitors
PARP inhibitor development is on the rise as more PARP family members emerge as novel drug targets in diseases such as cancer, inflammation, and viral infection. Understanding a drug's mechanism of action and potential risks for toxicity requires proteome-wide characterization of both on- and off-target engagement. This review will highlight different methods to map out the protein interaction profile of a small molecule, using the clinically approved PARP inhibitors as a case study. The approaches discussed here will mainly focus on chemoproteomic workflows, using inhibitor bead-conjugates and photoaffinity labeling probes, but will also touch on the utility of biochemical assays. Collectively, these strategies have revealed new targets for PARP inhibitors beyond the expected PARP1/2, providing valuable insights for understanding mechanism of action, toxicity, and polypharmacology.
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