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Title: Discovery of a new class of Cathepsin K inhibitors in Rhizoma Drynariae as potential candidates for the treatment of Osteoporosis
Authors: Qiu, ZC
Dong, XL 
Dai, Y
Xiao, GK
Wang, XL
Wong, KC 
Wong, MS 
Yao, X
Keywords: Bone resorption
Cathepsin K
In silico target fishing
Kushennol F
RAW264.7 cells
Rhizoma Drynariae
Sophoraflavanone G
Issue Date: 2016
Publisher: Molecular Diversity Preservation International (MDPI)
Source: International journal of molecular sciences, 2016, v. 17, no. 12, 2116 How to cite?
Journal: International journal of molecular sciences 
Abstract: Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk.
ISSN: 1661-6596
EISSN: 1422-0067
DOI: 10.3390/ijms17122116
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