• Title/Summary/Keyword: Chemical library

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Characterization of Preclinical in Vitro and in Vivo Pharmacokinetic Properties of KPLA-012, a Benzopyranyl 1,2,3-Triazole Compound, with Anti-Angiogenetic and Anti-Tumor Progressive Effects

  • Nam, So Jeong;Lee, Taeho;Choi, Min-Koo;Song, Im-Sook
    • Mass Spectrometry Letters
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    • v.9 no.2
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    • pp.61-65
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    • 2018
  • KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent $HIF-1{\alpha}$ inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells ($3.1{\times}10^{-6}cm/s$) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effective pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.

Analysis of Essential Oil from Perennial Herbaceous Plants (다년생 초본류의 향기성분 분석)

  • Chung, Ha-Sook;Park, Jun-Yeon;Ahn, Young-Hee;Lee, Sang-Hyun;Shin, Kuk-Hyun
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.3
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    • pp.179-186
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    • 2009
  • The chemical composition of essential oil from the perennial herbaceous plants (Houttuynia cordata, Filipendula glaberrima, Peucedanum japonicum, and Ainsliaea acerifolia) was determined by GC/MS spectrometric analysis with the aid of NBS, Wiley Library and RI indice searches. The major constituents identified were $\alpha$-phellandrene (18.97%), $\gamma$-terpinene (12.32%), decanal (8.72%), 1-decanol (10.92%), decanoic acid (12.12%), and 2-undecanone (12.32%) from H. cordata, farnesol (2.83%), l-$\alpha$-terpineol (2.72%), benzenmethanol (2.03%), (Z)-3-hexen-1-ol (4.32%), and T-muurolol (2.07%) from F. glaberrima, $\alpha$-phellandrene (14.25%), endobornyl acetate (3.84%), heptanal (47.52%), octanal (2.65%), (E,E)-2,4-decadienal (2.75%), and octanoic acid (4.52%) from P. japonicum, and geyrene (9.74%), $\beta$-cubebene (11.15%), berkheyaradulen (22.32%), $\beta$-elemene (6.21%), (-)-A-selinene (4.85%), benzaldehyde (4.52%), and benzenacetaldehyde (3.40%) from A. acerifolia.

Cloning and Expression of Kluyveromyces fragilis $\beta$-Galactosidase Gene in Saccharomyces cerevisiae

  • Bang, Jeong-Hee;Nam, Doo-H.;Kang, Dae-Ook;Ahn, Jong-Seog;Ryu, Dewey-D.Y.
    • Journal of Microbiology and Biotechnology
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    • v.5 no.1
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    • pp.6-13
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    • 1995
  • A gene coding for the $\beta$-galactosidase (lactase) of Kluyveromyces tragilis UCD 55-55 was isolated by complementation in Escherichia coli YMC9. From the plasmid library made from Sau3A-digested chromosomal DNA, one positive clone was selected. The cloned gene for $\beta$-galactosidase was on 7.3 kilobase pair DNA fragment, and a slightly low level of $\beta$-galactosidase enzyme activity was detecied in E. coli. It was also confirmed that the cloned gene comes from K. tragilis by DNA-DNA hybridization and immunochemical blotting experiments. In order to construct a new yeast strain having the metabolic ability for lactose, the cloned gene for K. tragilis $\beta$-galactosidase was inserted in yeast vector YEp24 and YRp17, and transformed into Saccharomyces cerevisiae YNN27 and Ml-2B. The yeast transformants showed the nearly the same $\beta$-galactosidase productivity as level of K. tragilis when uninduced, but these could not utilize lactose as a sole carbon source, presumably due to the lack of lactose transport system. Nevertheless, a slightly higher ethanol productivity was achieved by these transformants than S. cerevisiae or K. tragilis, in the medium containing glucose and lactose.

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Determining the stellar parameters of solar-like stars using synthetic spectra

  • Kang, Won-Seok;Lee, Sang-Gak
    • The Bulletin of The Korean Astronomical Society
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    • v.36 no.2
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    • pp.151.2-151.2
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    • 2011
  • IGRINS (Immersion GRating INfrared Spectrometer) will provide the spectra with high-resolution and an instantaneous spectral coverage of H and K band in NIR region. Therefore, it is expected that the wide coverage of wavelength would make a production of an extensive NIR high-resolution spectra of standard stars as a prior program of IGRINS. As a counter part of these NIR spectra, we have planned to obtain the high-resolution spectra of those standard stars in optical band. These optical high-resolution spectra would give us an opportunity to produce the library of high-resolution stellar spectra covering from optical to NIR band, and to confirm the method to determine the stellar parameters and chemical abundances from the NIR high-resolution spectra. Before using the NIR high-resolution spectra, we have tested the method to determine the stellar parameters by comparing between the observed spectra and the synthetic spectra in optical band. In order to make the synthetic spectra, we have used the Kurucz ATLAS9 model grids and the SYNTH code described by Fiorella Castelli (http://wwwuser.oat.ts.astro.it/castelli/). For the cross-check against the parameters that would be derived from the NIR spectra, the stellar parameters such as effective temperature and surface gravity were determined using the optical spectra of the solar-like stars, as preliminary results.

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Development of New Dihydropyran Linker for Solid-Phase Reaction

  • Ryu, Joon-Hyung;Jeong, Jin-Hyun
    • Archives of Pharmacal Research
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    • v.22 no.6
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    • pp.585-591
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    • 1999
  • The linker which plays a role in connecting a polymer with a scaffold has become an important part n solid-phase reaction. To develop a new linker for alcohols and carbohydrates, dihydropyran moiety was selected in this study. New linker, 1-($4^{l},5^{l}$-dihydro-5H-pyranyl)-7-hydroxyheptan-3-one (5) was synthesized via four steps from $\delta$-valerolactone. This can be called as DDHP-linked Wang resin due to double dihy-dropyran rings. To the one pyran ring of new linker 5 was added Wang resin and other alcohols and carbohydrates as scaffolds were then added successfully to the another pyran ring. Carbohydrate and hydroxyl resins were connected via new linker in a 70% loading yield. The detachment of glucose moiety in the presence of PPTS (2 equiv.) in 1:1 n-buteanol/1,2-dichloroethane at $60^{\circ}C$ for 12 h was carried out quantitatively. When certain combinatorial chemical works are carried out using this dihydropyran linker, Wang resin itself can be recovered. Its fact is particularly very important in industry, because recovered resins can be recycled.

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Agonist (P1) Antibody Converts Stem Cells into Migrating Beta-Like Cells in Pancreatic Islets

  • Eun Ji Lee;Seung-Ho Baek;Chi Hun Song;Yong Hwan Choi;Kyung Ho Han
    • Journal of Microbiology and Biotechnology
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    • v.32 no.12
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    • pp.1615-1621
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    • 2022
  • Tissue regeneration is the ultimate treatment for many degenerative diseases, however, repair and regeneration of damaged organs or tissues remains a challenge. Previously, we showed that B1 Ab and H3 Ab induce stem cells to differentiate into microglia and brown adipocyte-like cells, while trafficking to the brain and heart, respectively. Here, we present data showing that another selected agonist antibody, P1 antibody, induces the migration of cells to the pancreatic islets and differentiates human stem cells into beta-like cells. Interestingly, our results suggest the purified P1 Ab induces beta-like cells from fresh, human CD34+ hematopoietic stem cells and mouse bone marrow. In addition, stem cells with P1 Ab bound to expressed periostin (POSTN), an extracellular matrix protein that regulates tissue remodeling, selectively migrate to mouse pancreatic islets. Thus, these results confirm that our in vivo selection system can be used to identify antibodies from our library which are capable of inducing stem cell differentiation and cell migration to select tissues for the purpose of regenerating and remodeling damaged organ systems.

Variations and Characters of Water Quality during Flood and Dry Seasons in the Eastern Coast of South Sea, Korea (한국 남해 동부 연안 해역에서 홍수기와 갈수기 동안 수질환경 특성과 변동)

  • Jeong, Do Hyeon;Shin, Hyeon Ho;Jung, Seung Won;Lim, Dhong Il
    • Korean Journal of Environmental Biology
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    • v.31 no.1
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    • pp.19-36
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    • 2013
  • Physiochemical characters of sea waters during summer flood- and winter dry-seasons and their spatial variations were investigated along the coastal area off the eastern South Sea, Korea. Using the hierarchical clustering method, in this study, we present comprehensive analyses of coastal waters masses and their seasonal variations. The results revealed that the coastal water of the study area was classified into six water masses (A to F). During summer season, the surface water was mainly occupied by the coastal pseudo-estuarine water (water mass B) with low salinity and high nutrients and the river-dominated coastal water (water mass C) with low nutrients, respectively. The bottom water was dominated by cold water (water mass D) with very low temperature, high salinity and high nutrients, compared to masses of surface water. Notably, the water mass B, with high concentrations of nutrients (silicate and nitrogen) and low salinity, which is strongly controlled by the water quality of river freshwater, seems to play an important role in controlling the water quality and further regulating physical processes on ecosystem in the eastern coastal area of South Sea. The water mass D (bottom cold water) coupled with a strong thermocline, which exists in near-bottom layer along the western margin of Korea Strait, has a low temperature, pH and DO, but abundant nutrients. This water mass disappears in winter owing to strong vertical mixing, and subsequently may act as a pool for nutrients during winter dry-season. On the other hand, vertically well-mixed water column during the winter season was typically occupied by the Tsushima (water mass E) and the coastal water (water mass F) with a development of coastal front formed in a transition zone between them. These winter water masses were characterized by low nutrient concentration and balance in N/P ratio, compared with summer season with high nutrient concentrations and strong N-limitation. Accordingly, the analysis of water masses will help one to better chemical and biological processes in coastal area. In most of the study area, characteristically, the growth of phytoplankton community is limited by nitrogen, which is clearly different with coastal environment of West Sea of Korea, with a relative lack of phosphorus. It showed the western and the southern coasts in Korea are substantially different from each other in environmental and ecological characteristics.

Dammarane-type triterpene oligoglycosides from the leaves and stems of Panax notoginseng and their antiinflammatory activities

  • Li, Juan;Wang, Ru-Feng;Zhou, Yue;Hu, Hai-Jun;Yang, Ying-Bo;Yang, Li;Wang, Zheng-Tao
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.377-384
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    • 2019
  • Background: Inflammation is widespread in the clinical pathology and closely associated to the progress of many diseases. Triterpenoid saponins as a key group of active ingredients in Panax notoginseng (Burk.) F.H. Chen were demonstrated to show antiinflammatory effects. However, the chemical structures of saponins in the leaves and stems of Panax notoginseng (PNLS) are still not fully clear. Herein, the isolation, purification and further evaluation of the antiinflammatory activity of dammarane-type triterpenoid saponins from PNLS were conducted. Methods: Silica gel and reversed-phase C8 column chromatography were used. Furthermore, preparative HPLC was used as a final purification technique to obtain minor saponins with high purities. MS, NMR experiments, and chemical methods were used in the structural identifications. The antiinflammatory activities of the isolated saponins were assessed by measuring the nitric oxide production in RAW 264.7 cells stimulated by lipopolysaccharides. Real-time reverse transcription polymerase chain reaction was used to measure the gene expressions of inflammation-related gene. Results: Eight new minor dammarane-type triterpene oligoglycosides, namely notoginsenosides LK1-LK8 (1-8) were obtained from PNLS, along with seven known ones. Among the isolated saponins, gypenoside IX significantly suppressed the nitric oxide production and inflammatory cytokines including tumor necrosis $factor-{\alpha}$, interleukin 10, interferon-inducible protein 10 and $interleukin-1{\beta}$. Conclusion: The eight saponins may enrich and expand the chemical library of saponins in Panax genus. Moreover, it is reported for the first time that gypenoside IX showed moderate antiinflammatory activity.

A Model for Radiological Dose Assessment in an Urban Environment (도시환경에서 방사성물질 오염에 따른 선량평가모델)

  • Hwang, Won-Tae;Kim, Eun-Han;Jeong, Hyo-Joon;Suh, Kyung-Suk;Han, Moon-Hee
    • Journal of Radiation Protection and Research
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    • v.32 no.1
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    • pp.1-8
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    • 2007
  • A model for radiological dose assessment in an urban environment, METRO-K has been developed. Characteristics of the model are as follows ; 1) mathematical structures are simple (i.e. simplified input parameters) and easy to understand due to get the results by analytical methods using experimental and empirical data, 2) complex urban environment can easily be made up using only 5 types of basic surfaces, 3) various remediation measures can be applied to different surfaces by evaluating the exposure doses contributing from each contamination surface. Exposure doses contributing from each contamination surface at a particular location of a receptor were evaluated using the data library of kerma values as a function of gamma energy and contamination surface. A kerma data library was prepared fur 7 representative types of Korean urban buildings by extending those data given for 4 representative types of European urban buildings. Initial input data are daily radionuclide concentration in air and precipitation, and fraction of chemical type. Final outputs are absorbed dose rate in air contributing from the basic surfaces as a function of time following a radionuclide deposition, and exposure dose rate contributing from various surfaces constituting the urban environment at a particular location of a receptor. As the result of a contaminative scenario for an apartment built-up area, exposure dose rates show a distinct difference for surrounding environment as well as locations of a receptor.