• BMB Reports
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• 제40권1호
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• pp.1-6
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• 2007

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogenactivated protein kinase (MAPK) kinase kinase that activates JNK and p38 kinases. ASK1 is activated by various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx which are thought to be responsible for the pathogenesis or exacerbations of various human diseases. Recent studies revealed the involvement of ASK1 in ROS- or ER stressrelated diseases, suggesting that ASK1 may be a potential therapeutic target of various human diseases. In this review, we focus on the current findings for the relationship between pathogenesis and ASK1-MAPK pathways.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2001년도 제2회 생물정보학 국제심포지엄
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• pp.139-149
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• 2001

Since 1990, the National Cancer Institute(NCI) has screened more than 60.000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI$_{50}$) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460, 000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.s.

• 통합자연과학논문집
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• 제9권4호
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• pp.268-274
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• 2016

Filariasis causing nematode Brugia malayi is shown to harbor wolbachia bacteria as symbionts. The sequenced genome of the wolbachia endosymbiont from B.malayi (wBm) offers an unprecedented opportunity to identify new wolbachia drug targets. Hence the enzyme carbonic anhydrase from wolbachia endosymbiont of Brugia malayi (wBm) which is responsible for the reversible interconversion of carbon dioxide and water to bicarbonate and protons (or vice versa) is chosen as the drug target for filariasis. This enzyme is thought to play critical functions in bacteria by involving in various steps of their life cycle which are important for survival, The 3D structure of wBm carbonic anhydrase is predicted by selecting a suitable template using the similarity search tool, BLAST. The BLAST results shows a hexapeptide transferase family protein from Anaplasma phagocytophilum (PDB ID: 3IXC) having 77% similarity and 54% identity with wBm carbonic anhydrase. Hence the above enzyme is chosen as the template and the 3D structure of carbonic anhydrase is predicted by the tool Modeller9v7. Since the three dimensional structure of carbonic anhydrase from wolbachia endosymbiont of Brugia malayi has not yet solved, attempts were made to predict this protein. The predicted structure is validated and also molecular docking studies are carried out with the suitable inhibitors that have been solved experimentally.

• Journal of Preventive Medicine and Public Health
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• 제42권6호
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• pp.371-376
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• 2009

In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.114-114
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• 2022

Excessive endogenous endotoxin, especially lipopolysaccharide (LPS) reflux from gastrointestinal (GI) tract to the liver tissue is one of the most serious reasons of severe and acute liver injury which is mainly mediated by Kupffer cell activations. However, there is no clear molecular clues to explain the exact pathophysiological mechanism and effective drugs available till nowadays. We aimed to comprehend the pathophysiological features of LPS-induced liver injury and evaluate the efficacies of potential therapeutic drug, Ga-mi-Yuk-Mi-Jihwang-Tang (GYM), which is composed of herbal plants. GYM remarkably caused to normalize hepatic inflammation and oxidations against LPS-induced liver injury by evidence of serum liver enzymes, histopathological analysis, both hepatic protein and gene expression levels of pro-inflammatory cytokines, nitric oxide levels, and hepatic tissue levels of reactive oxygen species (ROS) levels, malondialdehyde (MDA), and 4-hydroxyneoneal, respectively. To assess molecular events in the hepatic tissue, we further found hepatic Sirtuin6 (Sirt6) levels were considerably depleted by LPS injection with aberrant alterations of Nrf2/HO-1 signaling pathways, whereas administration with GYM notably exerted to normalize these abnormalities. Our results exhibited that GYM would be one of target drug to diminish hepatic inflammation as well as oxidative stress by regulation of hepatic Sirt6 levels.

• 대한한의학회지
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• 제45권1호
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• pp.114-125
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• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

• 약학회지
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• 제52권6호
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• pp.466-470
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• 2008

Human cytomegalovirus expresses an unusual protein kinase UL97, a member of ${H_V}{U_L}$ family of protein kinase. UL97 can phosphorylate nucleoside analogs such as ganciclovir as well as protein/peptide. It has previously been reported that UL97 is able to phosphorylate a KESYSVYVYKV peptide and that P+5 position (K) is important. We examined the extent of contribution of other positions (P-4 through P+6) of the peptide to be substrate of UL97 using alanine substituted peptides (Ala scanning) and deleted peptides. The result suggested that the E (P-2) is negative effect and P+5 (K) is still important. The peptide YSVYVYK is the shortest substrate enough to show high activity, which could be a starting point to develop peptidomimetic drug. This study would give important information to deeply understand the substrate specificity of UL97 and develop an antiviral drug using the small peptide identified here.

• Molecules and Cells
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• 제40권5호
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• pp.322-330
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• 2017

This study investigated the role of cancer/testis antigen DDX53 in regulating cancer stem cell-like properties. DDX53 shows co-expression with CD133, a marker for cancer stem cells. DDX53 directly regulates the SOX-2 expression in anti-cancer drug-resistant $Malme3M^R$ cells. DDX53 and miR-200b were found to be involved in the regulation of tumor spheroid forming potential of Malme3M and $Malme3M^R$ cells. Furthermore, the self-renewal activity and the tumorigenic potential of $Malme3M^R$-CD133 (+) cells were also regulated by DDX53. A miR-200b inhibitor induced the direct regulation of SOX-2 by DDX53 We therefore, conclude that DDX53 may serve as an immunotherapeutic target for regulating cancer stem-like properties of melanomas.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.262-266
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• 1999

Dopamine transporter (DAT) plays the most important role in terminating the actions of dopamines released into the synaptic cleft. DAT is also the target of various psychotropic drugs such as cocaine and amphetamine. In this study were prepared DAT-specific antibodies using the 2nd extracellular loop of rat DAT as an antigen. The 2nd extracellular loop of the rat DAT was expressed in bacterial as a fusion protein with glutathione-S-transferase, and injected ito rabbits to raise antibodies. Produced antibodies clearly recognized the rat DAT in ELISA, immunoblotting, and immumoprecipitation. As expected from the high sequence homology between the rat and human DAT, the antibodies raised for the rat DAT cross-reacted with the human DAT in the immunoblotting. Considering the specificity for DAT with wide range of applications such as ELISA, immunoblotting, and immunoprecipitation, these antibodies would be valuable tool for understanding the pharmacological actions of dopamine transporter and drug addition.

• Molecules and Cells
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• 제46권1호
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• pp.10-20
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• 2023

Antisense oligonucleotide (ASO) technology has become an attractive therapeutic modality for various diseases, including Mendelian disorders. ASOs can modulate the expression of a target gene by promoting mRNA degradation or changing pre-mRNA splicing, nonsense-mediated mRNA decay, or translation. Advances in medicinal chemistry and a deeper understanding of post-transcriptional mechanisms have led to the approval of several ASO drugs for diseases that had long lacked therapeutic options. For instance, an ASO drug called nusinersen became the first approved drug for spinal muscular atrophy, improving survival and the overall disease course. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Although Trikafta and other CFTR-modulation therapies benefit most CF patients, there is a significant unmet therapeutic need for a subset of CF patients. In this review, we introduce ASO therapies and their mechanisms of action, describe the opportunities and challenges for ASO therapeutics for CF, and discuss the current state and prospects of ASO therapies for CF.