• Biomolecules & Therapeutics
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• 제24권5호
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• pp.453-468
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• 2016

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.

• 한국정보시스템학회지:정보시스템연구
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• 제25권4호
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• pp.1-21
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• 2016

Purpose The study analyzed the factors affecting continuance use and self-disclosure in the SNS(social networking service) context based on a dual-factor model. As SNS users have concerned privacy for a long time, privacy concern affects continuous use and self-disclosure. In details, concern over privacy may have a stronger effect on self-disclosure than on continuance use as users' personal information can be more exposed during posting their dailies and photos. Design/Methodology/Approach SNS benefits, trust in SNS providers, and social influence are served as the key enablers and privacy concern as the inhibitor. Moreover, the relative impacts of SNS benefits and privacy concern on continuance use and self-disclosure were analysed in this study. From the data of 327 Facebook users, the researchers tested proposed theoretical model by using PLS. Findings Users' continuance intention and self-disclosure behavior are differently affected by different antecedents. Trust in SNS provider had a significant effect on self-disclosure intention, while it has no significant effect on continuance intention. Concern over privacy was negatively related to self-disclosure intention, while it was positively associated with continuance intention.

• 한국표면공학회지
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• 제53권3호
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• pp.124-129
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• 2020

This study is for the development of high temperature ALD SiO₂ film process, optimized for gap-fill process in manufacturing memory products, using a space-divided PE-ALD system equipped with an independent control dual plasma system and orbital moving unit. Space divided PE-ALD System has high productivity, and various applications can be applied according to Top Lid Design. But space divided ALD system has a limitation to realize concentric deposition map due to process influence due to disk rotation. In order to solve this problem, we developed an orbit rotation moving unit in which disk and wafer. Also we used Independent dual plasma system to enhance thin film properties. Improve productivity and film density for gap-fill process by having deposition and surface treatment in one cycle. Optimize deposition process for gap-fill patterns with different depths by utilizing our independently controlled dual plasma system to insert N₂and/or He plasma during surface treatment, Provide void-free gap-fill process for high aspect ratio gap-fill patterns (up to 50:1) with convex curvature by adjusting deposition and surface treatment recipe in a cycle.

• Bulletin of the Korean Chemical Society
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• 제35권9호
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• pp.2655-2659
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• 2014

Dual specificity protein phosphatase 4 (DUSP4) has been considered a promising target for the development of therapeutics for various human cancers. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule DUSP4 inhibitors. As a consequence of the virtual screening with the modified scoring function to include an effective molecular solvation free energy term, five micromolar DUSP4 inhibitors are found with the associated $IC_{50}$ values ranging from 3.5 to $10.8{\mu}M$. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of DUSP4 are discussed in detail.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권1호
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• pp.59-70
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• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.