Figshare最新文献

筛选

英文中文

Proteolysis-TargetingnChimera (PROTAC) Modificationnof Dovitinib Enhances the Antiproliferative Effect against FLT3-ITD-PositivenAcute Myeloid Leukemia Cells 非Dovitinib蛋白水解靶向嵌合体（PROTAC）修饰增强对flt3 - itd阳性急性髓系白血病细胞的抗增殖作用

Figshare Pub Date : 2021-10-25 DOI: 10.1021/acs.jmedchem.1c00996.s002

Sheng Cao (215934), Lan Ma (112478), Yulin Liu (457083), Mingming Wei (1454854), Yuhong Yao (10812038), Chen Li (54018), Ruonan Wang (4470499), Ning Liu (168279), Zhiqiang Dong (167671), Xuechun Li (11328711), Ming Li (91180), Xiaoji Wang (692235), Cheng Yang (273624), Guang Yang (154978)

{"title":"Proteolysis-TargetingnChimera (PROTAC) Modificationnof Dovitinib Enhances the Antiproliferative Effect against FLT3-ITD-PositivenAcute Myeloid Leukemia Cells","authors":"Sheng Cao (215934), Lan Ma (112478), Yulin Liu (457083), Mingming Wei (1454854), Yuhong Yao (10812038), Chen Li (54018), Ruonan Wang (4470499), Ning Liu (168279), Zhiqiang Dong (167671), Xuechun Li (11328711), Ming Li (91180), Xiaoji Wang (692235), Cheng Yang (273624), Guang Yang (154978)","doi":"10.1021/acs.jmedchem.1c00996.s002","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.1c00996.s002","url":null,"abstract":"Acutenmyeloid leukemia (AML) refers to one of the most lethal bloodnmalignancies worldwide. FLT3-ITD mutation is recognized as the mostncommon one that predicted a poorer prognosis. There have been manynprominent FLT3-ITD inhibitors approved by the FDA for clinical therapies.nHowever, as impacted by undesirable off-target effects, differentiatednmetabolic issues, and clinical drug resistance problems, it remainsnchallenging to discover alternative and promising solutions for treatingnFLT3-ITD+ AML. In this study, dovitinib was chemicallynmodified and converted into CRBN-recruiting PROTACs. Two active compoundsnwere identified, which showed enhanced antiproliferative effects againstnFLT3-ITD+ AML cells, both in vitro and in vivo. As demonstrated from further biological evaluation,nthe compounds could induce the degradation of the FLT3-ITD and KITnproteins in a ubiquitin–proteasome-dependent manner and completelynblock their downstream signaling pathway. The findings of this studynwould provide another promising strategy to develop novel therapiesnfor FLT3-ITD+ AML.","PeriodicalId":522908,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147906009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0