• Journal of the Korean Chemical Society
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• v.52 no.3
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• pp.266-272
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• 2008

• Bulletin of the Korean Chemical Society
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• v.32 no.12
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• pp.4165-4166
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• 2011

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2305-2310
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• 2013

A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an $IC_{50}$ value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.

• Genomics & Informatics
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• v.17 no.2
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• pp.18.1-18.10
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• 2019

Prediction of the relations among drug and other molecular or social entities is the main knowledge discovery pattern for the purpose of drug-related knowledge discovery. Computational approaches have combined the information from different sources and levels for drug-related knowledge discovery, which provides a sophisticated comprehension of the relationship among drugs, targets, diseases, and targeted genes, at the molecular level, or relationships among drugs, usage, side effect, safety, and user preference, at a social level. In this research, previous work from the BioNLP community and matrix or matrix decomposition was reviewed, compared, and concluded, and eventually, the BioNLP open-shared task was introduced as a promising case study representing this area.

• Applied Microscopy
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• v.51
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• pp.13.1-13.7
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• 2021

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has arisen as a global pandemic affecting the respiratory system showing acute respiratory distress syndrome (ARDS). However, there is no targeted therapeutic agent yet and due to the growing cases of infections and the rising death tolls, discovery of the possible drug is the need of the hour. In general, the study for discovering therapeutic agent for SARS-CoV-2 is largely focused on large-scale screening with fragment-based drug discovery (FBDD). With the recent advancement in cryo-electron microscopy (Cryo-EM), it has become one of the widely used tools in structural biology. It is effective in investigating the structure of numerous proteins in high-resolution and also had an intense influence on drug discovery, determining the binding reaction and regulation of known drugs as well as leading the design and development of new drug candidates. Here, we review the application of cryo-EM in a structure-based drug design (SBDD) and in silico screening of the recently acquired FBDD in SARS-CoV-2. Such insights will help deliver better understanding in the procurement of the effective remedial solution for this pandemic.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.3-6
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• 2001

Inflammation is an outcome or an end effect of disruption of complex immunological balance. A variety of approaches to control immunological unbalance have been tried, and some of them are in practice in the clinic. Since inflammatory disorders are reflection of very complex immunological responses, it should be difficult to have such disorders under complete control. Thus, most of the drugs, being marketed and under development, possess some degrees of undesired side offsets originating from disruption of immunological balance. Steroids are excellent drugs suppressing inflammation in short term, however, long-term use of steroids would incur a serious side effect of "rebound". Another example is TNF-${\alpha}$-neutralizing agents, such as enbrel and infliximab. TNF-${\alpha}$ has been known to play a key role in the exacerbation of inflammation, and knock-out of TNF-${\alpha}$ is regarded essential to control of chronic inflammation. The TNF-${\alpha}$-neutralizing drugs in the market are regarded very efficient in the management of rheumatoid arthritis. Upon long term use, however, those drugs cause sepsis to a certain proportion of patients. It is ironical that a high plasma level of TNF-${\alpha}$ is known to be responsible for sepsis, and that the drugs scavenging TNF-${\alpha}$ cause sepsis. The above two examples illustrate well the difficulty of discovering an anti-inflammatory drug without unwanted immunological side effects. An anti-inflammatory drug would make a case in the market, as long as the drug has huge therapeutic benefits compared to its expected but unwanted immunological side effects, where cyclooxygenase-2 inhibitors are positioning. In this presentation, will be discussed general aspects of cyclooxygenase-2 inhibition in conjunction with 3(2Η)furanone derivatives, a novel class of COX-2 inhibitors.

• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.250-252
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• 2014

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

• The Plant Pathology Journal
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• v.33 no.6
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• pp.529-542
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• 2017

Control of plant diseases is largely dependent on use of agrochemicals. However, there are widening gaps between our knowledge on plant diseases gained from genetic/mechanistic studies and rapid translation of the knowledge into target-oriented development of effective agrochemicals. Here we propose that the time is ripe for computer-aided drug discovery/design (CADD) in molecular plant pathology. CADD has played a pivotal role in development of medically important molecules over the last three decades. Now, explosive increase in information on genome sequences and three dimensional structures of biological molecules, in combination with advances in computational and informational technologies, opens up exciting possibilities for application of CADD in discovery and development of agrochemicals. In this review, we outline two categories of the drug discovery strategies: structure- and ligand-based CADD, and relevant computational approaches that are being employed in modern drug discovery. In order to help readers to dive into CADD, we explain concepts of homology modelling, molecular docking, virtual screening, and de novo ligand design in structure-based CADD, and pharmacophore modelling, ligand-based virtual screening, quantitative structure activity relationship modelling and de novo ligand design for ligand-based CADD. We also provide the important resources available to carry out CADD. Finally, we present a case study showing how CADD approach can be implemented in reality for identification of potent chemical compounds against the important plant pathogens, Pseudomonas syringae and Colletotrichum gloeosporioides.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2385-2390
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• 2014

Novel 2,6-difuctionalized 2H-benzopyrans were synthesized and evaluated for a sphingosylphosphorylcholine(SPC) inhibitor. The synthetic 2H-benzopyrans 1c and 3a showed high potency in SPC-induced cell proliferation assay ($IC_{50}$ < 20 nM). Neither hERG $K^+$ channel binding (> $10{\mu}M$) nor CYP inhibitions (> $10{\mu}M$) were observed. Also, the simple structure-activity relationship (SAR) results were obtained from analysis of 2H-benzopyran derivatives 1-3 and the anti-SPC effect of 2H-benzopyran 1c was confirmed by a HUVEC tube formation assay.

• Archives of Pharmacal Research
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• v.21 no.2
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• pp.89-105
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• 1998

In the past decade, significant progress has been achieved in the battle against hepatitis B virus. In addition to the immunomodulating agents such as interferon-.alpha., and thymosin, many novel antiviral agents have been discovered, among which nucleoside analogues are the mainstay. New-generation compounds such as 3TC and famciclovir have shown promise in the treatment of patients chronically infected by this virus, and are on the line for approval. However, viral rebound after cessation of therapy still remains a major problem. Additionally, the reports on the drug resistance to these antiviral agents suggest that combination therapy will be the eventual strategy (Bartholomew et al., 1997; Tipples et al., 1996). Therefore, developments of safe and effective antiviral agents which do not cross-resist with currently available antiviral drugs are still much needed.