biostudies-literatureUnknown10(11)Shi CTargeting oncogenic proteins for degradation using proteolysis-targeting chimera (PROTAC) recently has drawn increasing attention in the field of cancer research. Bromodomain and extra-terminal (BET) family proteins are newly identified cancer-related epigenetic regulators, which have a role in the pathogenesis and progression of osteosarcoma. In this study, we investigated the in vitro and in vivo anti-osteosarcoma activity by targeting BET with a PROTAC molecule BETd-260. The results showed that BETd-260 completely depletes BET proteins and potently suppresses cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. Compared with BET inhibitors HJB-97 and JQ1, the activity of BETd-260 increased over 1000 times. Moreover, BETd-260 substantially inhibited the expressiCell death & disease815https://www.ebi.ac.uk/biostudies/studies/S-EPMC6814818biostudies-literaturePROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis.PMC6814818Wang PShi CZhang YZhang HXu DWang HZhang SYin LWang KfalsePROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis.Targeting oncogenic proteins for degradation using proteolysis-targeting chimera (PROTAC) recently has drawn increasing attention in the field of cancer research. Bromodomain and extra-terminal (BET) family proteins are newly identified cancer-related epigenetic regulators, which have a role in the pathogenesis and progression of osteosarcoma. In this study, we investigated the in vitro and in vivo anti-osteosarcoma activity by targeting BET with a PROTAC molecule BETd-260. The results showed that BETd-260 completely depletes BET proteins and potently suppresses cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. Compared with BET inhibitors HJB-97 and JQ1, the activity of BETd-260 increased over 1000 times. Moreover, BETd-260 substantially inhibited the expressi2019-01-01T00:00:00Z2019 Oct2025-04-05T13:18:56.624Z2019-11-07T08:07:30ZS-EPMC68148183165382610.1038/s41419-019-2022-2