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Identification of Osteogenic Purmorphamine Derivatives  

Lee, Sung-Jin (Department of Animal Life Resource Science, Kangwon National University)
Lee, Hak-Kyo (Gyeonggi Regional Research Center, Hankyong National University)
Cho, Sung Yun (Drug Discovery Division, Korea Research Institute of Chemical Technology)
Choi, Joong-Kwon (Drug Discovery Division, Korea Research Institute of Chemical Technology)
Shin, Hea Kyeong (Department of Plastic Surgery, College of Medicine, Dongguk University)
Kwak, Eun-Jung (Department of Biochemistry, College of Medicine, Chungbuk National University)
Cho, Mi-Ran (Department of Biochemistry, College of Medicine, Chungbuk National University)
Kim, Hye-Ryun (Department of Biochemistry, College of Medicine, Chungbuk National University)
Kim, Seung-Ryol (Department of Biochemistry, College of Medicine, Chungbuk National University)
Kim, Yong-Min (Department of Orthopaedic Surgery, College of Medicine, Chungbuk National University)
Park, Kyoung-Jin (Department of Orthopaedic Surgery, College of Medicine, Chungbuk National University)
Choi, Joong-Kook (Department of Biochemistry, College of Medicine, Chungbuk National University)
Publication Information
Molecules and Cells / v.26, no.4, 2008 , pp. 380-386 More about this Journal
Abstract
During embryonic and cancer development, the Hedgehog family of proteins, including Sonic Hedgehog, play an important role by relieving the inhibition of Smo by Ptc, thus activating the Smo signaling cascade. Recently, a purine compound, purmorphamine, has been reported to target the Hedgehog signaling pathway by interacting with Smo. Interestingly, both Sonic Hedgehog and purmorphamine were found to promote the osteogenic differentiation of mouse chondroprogenitor cells. However, there is insufficient information as to how the activation of this seemingly unrelated signaling pathway, either by Sonic Hedgehog or purmorphamine, contributes to osteogenesis. Using alkaline phosphatase assays, we screened 125 purmorphamine derivatives from the Korea Chemical Bank for effects on the differentiation of preosteoblast C2C12 cells. Here, we report that two purine derivatives modulate ALP activity as well as the expression of genes whose expression is known or suggested to be involved in osteogenesis.
Keywords
alkaline phosphatase assay; C2C12 preosteoblasts; osteogenesis; purmorphamine; Sonic hedgehog;
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