title: Identification of osteogenic purmorphamine derivatives.
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.
authors.affiliation: Department of Animal Life Resource Science, Kangwon National University, Chuncheon, Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hak-Kyo
authors.initials: HK
authors.lastname: Lee
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Joong-Kwon
authors.initials: JK
authors.lastname: Choi
authors.forename: Hea Kyeong
authors.initials: HK
authors.lastname: Shin
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kwak
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Cho
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kim
authors.forename: Seung-Ryol
authors.initials: SR
authors.lastname: Kim
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Park
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011687:Purines / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009025:Morpholines; D011687:Purines; D007770:L-Lactate Dehydrogenase; C470893:purmorphamine