{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:37:25Z","timestamp":1790699845337,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502636"],"award-info":[{"award-number":["81502636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008871","name":"Yunnan Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["2017ZF010"],"award-info":[{"award-number":["2017ZF010"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["14DZ2294100"],"award-info":[{"award-number":["14DZ2294100"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,3]]},"abstract":"\n Poly(\n ADP<\/jats:styled-content>\n \u2010ribose) polymerase (\n PARP<\/jats:styled-content>\n ) enzymes play an important role in repairing\n DNA<\/jats:styled-content>\n damage and maintaining genomic stability. Olaparib, the first\u2010in\u2010class\n PARP<\/jats:styled-content>\n inhibitor, has shown remarkable clinical benefits in the treatment of\n \n BRCA<\/jats:styled-content>\n <\/jats:italic>\n \u2010mutated ovarian or breast cancer. However, the undesirable hematological toxicity and pharmacokinetic properties of olaparib limit its clinical application. Here, we report the first preclinical characterization of fluzoparib (code name:\n SHR<\/jats:styled-content>\n \u20103162), a novel, potent, and orally available inhibitor of\n PARP<\/jats:styled-content>\n . Fluzoparib potently inhibited\n PARP<\/jats:styled-content>\n 1 enzyme activity and induced\n DNA<\/jats:styled-content>\n double\u2010strand breaks, G\n 2<\/jats:sub>\n \/M arrest, and apoptosis in homologous recombination repair (\n HR<\/jats:styled-content>\n )\u2010deficient cells. Fluzoparib preferentially inhibited the proliferation of\n HR<\/jats:styled-content>\n \u2010deficient cells and sensitized both\n HR<\/jats:styled-content>\n \u2010deficient and\n HR<\/jats:styled-content>\n \u2010proficient cells to cytotoxic drugs. Notably, fluzoparib showed good pharmacokinetic properties, favorable toxicity profile, and superior antitumor activity in\n HR<\/jats:styled-content>\n \u2010deficient xenografts models. Furthermore, fluzoparib in combination with apatinib or with apatinib plus paclitaxel elicited significantly improved antitumor responses without extra toxicity. Based on these findings, studies to evaluate the efficacy and safety of fluzoparib (phase\n II<\/jats:styled-content>\n ) and those two combinations (phase I) have been initiated. Taken together, our results implicate fluzoparib as a novel attractive\n PARP<\/jats:styled-content>\n inhibitor.\n <\/jats:p>","DOI":"10.1111\/cas.13947","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T03:48:52Z","timestamp":1548042532000},"page":"1064-1075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Pharmacologic characterization of fluzoparib, a novel poly(\n ADP<\/scp>\n \u2010ribose) polymerase inhibitor undergoing clinical trials"],"prefix":"10.1111","volume":"110","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyong","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co Ltd Lianyungang China"},{"name":"Pharmaceutical Research Center and School of Chemistry and Chemical Engineering Southeast University Nanjing China"},{"name":"Jiangsu Province Hi\u2010Tech Key Laboratory for Biomedical Research Southeast University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengying","family":"Xie","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Medicine Co Ltd Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhao","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubin","family":"Bao","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Fu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7396-7122","authenticated-orcid":false,"given":"Liguang","family":"Lou","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 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