• Journal of Pharmaceutical Investigation
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• 제39권4호
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• pp.299-307
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• 2009

Data exclusivity is one of the most important intellectual property rights of pharmaceuticals. During data exclusivity period, third parties are prohibited from relying on the data which the original company has submitted to regulatory authority for drug application. I investigated data exclusivity systems for pharmaceuticals in the US, EU, Canada and Korea. New chemical entities were usually given the longest periods of data exclusivity compared to drugs with new indication or new formulation, although the protection periods varied by country. For new drugs to be entitled to a data exclusivity, strict conditions should be met. Data exclusivity has also been provided as an incentive to promote clinical investigation and drug development for pediatric population or orphan diseases. In Korea, data exclusivity was adopted in 1995 as an additive provision to "drug re-examination" which is to investigate post-marketing safety information of new drugs. It was introduced with few discussion on the purposes or effects of data exclusivity on pharmaceutical industry and pharmaceutical market in this country. I found that Korea's data exclusivity system falls short of considerations on valuing innovation of pharmaceutical research. It is necessary to improve data exclusivity system in order to promote innovative pharmaceutical development and to balance intellectual property rights protection and access to drugs in this country.

• 한국생산제조학회지
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• 제26권1호
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• pp.36-43
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• 2017

A drug infuser is a well-known device that is widely used in various areas of clinical practice. However, some materials used in the drug infuser have been developed for particular purposes and thus, their design characteristics have to be changed considerably. Especially, the implications of a new filler in the drug infuser have migrated to the areas of body corrections in plastic surgery. In this study, the design process of a drug infuser managing a large content volume has been studied from the perspective of structure safety. A new design of the drug infuser that uses a 10 cc filler with high viscosity is presented. Finite element analysis is used to confirm that the assembled drug infuser is safe enough to hold the required loading of 490 N. Furthermore, the final prototype of the drug infuser was successful in reducing the weight up to 400 g without compromising the safety.

• 통합자연과학논문집
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• 제9권2호
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• pp.113-120
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• 2016

Monopolar spindle 1 (Mps1) is an attractive cancer target due to its high expression levels in a wide range of cancer cells. Mps1 is a dual specificity kinase. It plays an essential role in mitosis. The high expression od Mps1 was observed in various grades of breast cancers. In the current study, we have developed a CoMFA model of pyridazine derivatives as Mps1 kinase inhibitors. The developed CoMFA model ($q^2=0.797$; ONC=6; $r^2=0.992$) exhibited a good predictive ability. The model was then validated by Leave out five, progressive sampling and bootstrapping and found to be robust. The analysis of the CoMFA contour maps depicted favorable and unfavorable regions to enhance the activity. Bulky positive substitution at $R^3$ position and Negative substitution in $R^1$ position is favored could increase the activity. In contrast, bulky substitution in $R^1$ position is not favored. Our results can be used in designing a potent Mps1 (TTK) inhibitor.

• 통합자연과학논문집
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• 제7권4호
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• pp.253-259
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• 2014

Protein kinase C theta (PKC-${\theta}$) is a serine/threonine specific protein kinase. It is largely expressed in the T-cells and CD28 signaling. PKC-${\theta}$ phosphorylates diverse proteins that are involved in the various cellular signaling pathways. Activated PKC-${\theta}$ in turn activates other transcription factors that control the proliferation and differentiation of T- cells. PKC-${\theta}$ is considered to be an interesting therapeutic target due to its crucial role in the proliferation, differentiation and survival of T-cells. In the present study, we have performed ligand-based CoMFA study on a series of pyridylpyrazolopyridine derivatives as PKC-${\theta}$ inhibitors. An acceptable CoMFA model ($q^2$=0.544; ONC=4; $r^2$=0.876) was developed and validated by Bootsrapping and progressive sampling. The CoMFA contour map suggested the regions to increase the activity. Bulky substitutions in R2 position of the piperizine ring could increase the activity. Similarly positive, small substitution in the R1 position of the Pyridine ring could considerably increase the activity. Our work could assist in designing more potent PKC-${\theta}$ inhibitors of pyridylpyrazolopyridine derivatives.

• 통합자연과학논문집
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• 제7권1호
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• pp.45-49
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• 2014

The (c-Jun N-terminal kinase 3) JNK3 is a potential therapeutic target for various neurological disorders. Here, a three dimensional quantitative structure-activity relationship (3D-QSAR) study on phenoxypyridine as JNK3 inhibitors was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The comparative molecular field analysis (CoMFA) using different partial atomic charges, was employed to understand the structural factors affecting JNK3 inhibitory potency. The Gasteiger-Marsili yielded a CoMFA model with cross-validated correlation coefficient ($q^2$) of 0.54 and non-cross-validated correlation coefficient ($r^2$) of 0.93 with five components. Furthermore, contour maps suggested that bulky substitution with oxygen atom in $R^3$ position could enhance the activity considerably. The work suggests that further chemical modifications of the compounds could lead to enhanced activity and could assist in the design of novel JNK3 inhibitors.

• Bulletin of the Korean Chemical Society
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• 제32권10호
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• pp.3752-3755
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• 2011

• Journal of Pharmaceutical Investigation
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• 제35권6호
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• pp.471-481
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• 2005

In Korea, generic drug and bioequivalence test are the hot issues since a new medical system of separation of dispensary from medical practice was started in 2000. The KFDA(Korea FDA) had revised several times ${\ulcorner}Guidance\;for\;bioequivalence\;test{\lrcorner}$. In vitro dissolution test has been extensively used as a quality control tool for solid oral dosage forms. In an effort to minimize unnecessary human testing, in vitro/in vivo correlations (IVIVC) between in vitro dissolution and in vivo bioavailability are increasingly becoming an integral part on extended release drug product development. The recently published US guidance, ${\ulcorner}Extended\;release\;oral\;dosage\;forms\;:\;development,\;evaluation,\;and\;application\;of\;in\;vitro/in\;vivo\;correlations{\lrcorner}$ will be helpful for us to make our own guideline.

• Parasites, Hosts and Diseases
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• 제52권4호
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• pp.345-353
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• 2014

Babesia gibsoni is an intraerythrocytic apicomplexan parasite that causes piroplasmosis in dogs. B. gibsoni infection is characterized clinically by fever, regenerative anemia, splenomegaly, and sometimes death. Since no vaccine is available, rapid and accurate diagnosis and prompt treatment of infected animals are required to control this disease. Over the past decade, several candidate molecules have been identified using biomolecular techniques in the authors' laboratory for the development of a serodiagnostic method, vaccine, and drug for B. gibsoni. This review article describes newly identified candidate molecules and their applications for diagnosis, vaccine production, and drug development of B. gibsoni.

• Molecules and Cells
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• 제41권4호
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• pp.320-330
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• 2018

${\delta}$-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that ${\delta}$-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind ${\delta}$-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that ${\delta}$-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase. c-Cbl monoubiquitinates EGFR and thus facilitates its internalization, followed by lysosomal degradation. We observed that ${\delta}$-catenin plays a key role in EGFR stability and downstream signaling. ${\delta}$-Catenin competes with c-Cbl for EGFR binding, which results in a reduction of binding between c-Cbl and EGFR and thus decreases the ubiquitination of EGFR. This in turn increases the expression of membrane bound EGFR and enhances EGFR/Erk1/2 signaling. Our findings add a new perspective on the role of ${\delta}$-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.97-102
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• 2002

Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.