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X609, a novel manassantin A derivative, exhibits antitumor activity in MG-63 human osteosarcoma cells in vitro and in vivo

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Manassantin A has been well-established as an inhibitor of HIF-1. In the present study, a new manasantin A derivative, X609, with decreased stereochemical complexity, rendering it amenable to a simplified synthesis scheme, was synthesized and was found to increase HIF1 inhibitory activity. X609 exhibited antiproliferative activity in a broad spectrum of tumor cell lines, via HIF1dependent mechanisms. X609 may induce apoptosis in MG63 cells through activation of the mitochondrial pathway. Oral administration of X609 significantly inhibited the growth of human osteosarcomas implanted into nude mice. In light of the results of the present study, it may be possible to develop X609 for use as a novel antitumor agent, which targets human osteosarcoma.
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Document Type: Research Article

Affiliations: 1: Department of Orthopedics, The Quanzhou Licheng Xingxian Hospital, Quanzhou 362005, P.R. China 2: Department of Orthopedics, Linyi People's Hospital, Linyi 276000, P.R. China 3: Department of Orthopedics, Shandong Provincial Hospital, Jinan 250021, P.R. China 4: Department of Orthopedics, The Jinan Military General Hospital, Jinan 250031, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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