• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.443-446
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• 2013

In this work, a novel strategy is provided to prepare silver nanoplates by a fibronectin (Fn) nanofibril template. First, Fn molecules were controlled to assemble into amyloid-like nanofibrils in highly concentrated ethanol aqueous solution. The resultant nanofibrils could serve as a soft template to direct the formation of silver nanoplates. It is worth noting that the silver nanoplates are excellent surface-enhanced Raman scattering (SERS) substrate with 4-aminothiophenol (4-ATP) molecule as a test probe. This high active SERS substrate can also be used to detect drug molecule, 2-thiouracil with high sensitivity.

• Journal of Biomedical Engineering Research
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• v.43 no.2
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• pp.94-101
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• 2022

Recent advancement of micro/nano technology enables the development of diverse micro/nano particle-based delivery systems. Due to the multi-functionality and engineerability, particle-based delivery system are expected to be a promising method for delivery to the target cell. Since the particle-based delivery system should be delivered to the various kinds of target cell, including the cardiovascular system, cancer cell etc., it is frequently decorated with multiple kinds of targeting molecule(s) to induce specific interaction to the target cell. The surface decorated molecules interact with the cell surface expressed molecule(s) to specifically form a firm adhesion. Thus, in this study, the probability of adhesion is estimated to predict the possibility to form a firm adhesion for the multi-ligand decorated particle-based delivery system.

• YAKHAK HOEJI
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• v.57 no.6
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• pp.412-419
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• 2013

Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.400-405
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• 2014

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.455-464
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• 2022

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.227-227
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• 1994

퀴놀론계 항균제란 퀴놀린 이나 나프티리딘 핵을 갖고 있는 화합물로써 항균효과를 나타내는 물질을 의미한다. 이러한 퀴놀론계 항균제의 구조적 특성에 따라 항균활성의 영향은 ASAR에 의하여 이미 구조적 제한성을 가지고 있다고 보고 되어있다. 본 연구에서는 Drug-Enzyme inleraetion domain을 변화시킴으로서 보다 강력한 항균제를 찾아낼수 있을 것으로 판단하고, 기존 항균제가 C-7에 piperazine이 있으므로 piperazine의 chemical isoster 또는 bioisoster의 개념하에서 C-7에 도입한 아민류를 분자설계하고 합성하여 새로운 퀴놀론계 항균제를 만들어 내고자 하였으며 target molecule은 다음 그림과 같다.

• Molecules and Cells
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• v.46 no.1
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• pp.65-67
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• 2023

SMILES (simplified molecular-input line-entry system) information of small molecules parsed by one-hot array is passed to a convolutional neural network called black box. Outputs data representing a gene signature is then matched to the genetic signature of a disease to predict the appropriate small molecule. Efficacy of the predicted small molecules is examined by in vivo animal models. GSEA, gene set enrichment analysis.

• Bulletin of the Korean Chemical Society
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• v.34 no.7
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• pp.2006-2010
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• 2013

Leukocyte common antigen-related phosphatase (LAR) has been considered a promising target for the development of therapeutics for neurological diseases. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule LAR inhibitors. Five of these inhibitors revealed micromolar inhibitory activities with the associated $IC_{50}$ values ranging from 2 to 6 ${\mu}M$. Because the 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 LAR are discussed in detail.

• Bulletin of the Korean Chemical Society
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• v.23 no.3
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• pp.391-394
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• 2002

Berberine and berberrubine, which display antitumor activity, have also demonstrated distinct enzyme-poisoning activities by stabilizing topoisomerase Ⅱ-DNA cleavable complexes. The protoberberine berberrubine differs in chemical structure with berberine at only one position, however, it shows a prominent activity difference from berberine. Solution structures of berberine and berberrubine determined by NMR spectroscopy are similar, however, the minor structural rearrangement has been observed near 19 methoxy or hydroxyl group. We suggest that the DNA cleavage activities of topoisomerase Ⅱ poisons could be correlated with both chemical environments and minor structural change together with hydrophobicity of interacting side chains of drugs with DNA molecule.

• Korean Journal of Pharmacognosy
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• v.28 no.2
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• pp.65-71
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• 1997

This study was carried out to purify and to characterize various bioactive material acemannan from Aloe vera. Purified acemannan was mannose (67%) and acetyl group (23%), and the rest of glucose was galactose that consists of long chain polydispered beta-(1, 4) linked mannan polymers. The sugar and acetyl group in the molecule were linked by molar ratio of 3 : 1. This polysaccharide from Aloe vera may provide functional flood and potential drug source with antiviral and immunomodulating properties.