• Genomics & Informatics
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• v.16 no.3
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• pp.44-51
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• 2018

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (-38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of $0.286{\mu}g/L$ against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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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.

• BMB Reports
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• v.43 no.6
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• pp.383-388
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• 2010

The number of cancer patients has increased due to longer life spans and treatment has become a universal problem. Since molecular-targeted therapies were introduced as a new developmental strategy, certain targets have been examined hundreds of times, with developers overlapping their research efforts. We need to focus our energy and resources on novel drug candidate identification and optimization, in order to enhance the entry of early-stage drug candidates into the therapeutics pipeline. This presents a major opportunity for Korea to jump the decades-old development gap between our programs and those that are more advanced in other countries. Although this country does not have a specific center for validation and development of cancer therapeutics, we do have cutting-edge scientists performing research in many institutions. In this paper, I will review cancer drug development in Korea and suggest future directions, while urging colleagues to utilize their networking expertise so we can move toward a new paradigm of novel therapeutics development. An example of such efforts has begun with the Drug Development Consortium, which was described in the KSBMB chapter. This consortium was launched in 2010 by biochemists, chemists, cell and molecular biologists and pharmacologists. It is clear that effective cancer therapeutics will be developed more efficiently when we all strive for the same goal.

• Korean Journal of Clinical Pharmacy
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• v.18 no.2
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• pp.84-96
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• 2008

In the recent, pharmacokinetic (PK)/pharmacodynamic (PD) modeling has appeared as a critical path tools in new drug development to optimize drug efficacy and safety. PK/PD modeling is the mathematical approaches of the relationships between PK and PD. This approach in new drug development can be estimated inaccessible PK and PD parameters, evaluated competing hypothesis, and predicted the response under new conditions. Additionally, PK/PD modeling provides the information about systemic conditions for understanding the pharmacology and biology. These advantages of PK/PD model development are to provide the early decision-making information in new drug development process, and to improve the prediction power for the success of clinical trials. The purpose of this review article is to summarize the PK/PD modeling process, and to provide the theoretical and practical information about widely used PK/PD models. This review also provides model schemes and the differential equations for the development of PK/PD model.

• Bulletin of the Korean Chemical Society
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• v.35 no.9
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• pp.2649-2654
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• 2014

Synthesis of north-5'-methylbicyclo[3.1.0]hexyl adenine and hypoxanthine nucleosides with an ethenyl group at C3' position was successfully achieved by a highly facile method. Methylbicyclo[3.1.0]hexanone (${\pm}$)-7 with three contiguous chiral centers and its epimer (${\pm}$)-6 was remarkably simply constructed only by four steps involving a carbenoid insertion reaction in the presence of rhodium (II) acetate dimer as a metal catalyst, giving a correct relative stereochemistry of the generated three chiral centers. Due to steric hindrance from the concave face of the bicyclo[3.1.0]hexanone system, a Grignard reaction of (${\pm}$)-7 with ethenylmagnesium bromide showed exclusive diastereoselectivity towards the b-face. The Grignard reaction chemoselectively proceeded without reacting with ester functionality. Coupling reaction of glycosyl donor (${\pm}$)-11 with 6-chloropurine nucleobase afforded only the desired $N^9$-alkylated nucleoside without the formation of $N^7$-regioisomer. By the conventional method, 6-chloro group was converted into 6-amino and 6-hydroxy groups to give the desired adenine and hypoxanthine bicyclo[3.1.0]hexyl carbanucleosides with 3'-ethenyl group, respectively.

• Molecules and Cells
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• v.41 no.4
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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.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.73-77
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• 2007

N,N-Dimethyl-D-ribo-phytosphingosine (DMPH) is an N-methyl derivative of sphingosine. In the present paper, we studied effects of DMPH on intracellular Ca$^{2+}$ concentration, pH, glutamate uptake, and cell viability in human 1321N1 astrocytes. DMPH increased intracellular Ca$^{2+}$ concentration and cytosolic pH significantly in a dose-dependent manner. DMPH also inhibited glutamate uptake by 1321N1 astrocytes. Finally, treatment of cells with DMPH for 24 h reduced viability of cells largely and concentration-dependently. In summary, DMPH increased intracellular Ca$^{2+}$ concentration and pH, inhibited glutamate uptake and evoked cytotoxicity in 1321N1 astrocytes. Our observations with DMPH in the 1321N1 astrocytes would enhance understanding of DMPH actions in the brain.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.410-415
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• 2008

Previously, we identified albumin as an inhibitory factor in serum for cell adhesion of T cells such as human Jurkat T and primary cultured human T cells. In the present study, we found that other hematopoietic cell lines including U-937 human monocytes, THP-1 human monocytes, K-562 promyelocytic leukemia cells, and HL-60 human leukemia cells, also adhere to tissue culture flasks when serum is withdrawn, and albumin exerts an inhibitory effect on cell adhesion by those cells, implying that this inhibition is a common phenomenon in hematopoietic cells. Furthermore, we found that cell adhesion is inhibited by antioxidants such as (-)-epigallocatechin- 3-gallate (EGCG), morin, and a-tocopherol. Our results suggest that albumin may inhibit basal cell adhesion of hematopoietic cells and that the oxidative balance in the plasma may be important for cell adhesion of hematopoietic cells in vivo.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.135-140
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• 1994

Over past decades, numerous in vitro model has been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as : 1. the characterization of main biotransformation reactions. 2. the identification of phase I and phase II isozymes involved in such reactions 3. the evaluation of interspecies differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles 4. the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions 5. the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obstained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers.

• YAKHAK HOEJI
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• v.55 no.4
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• pp.345-351
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• 2011

Gastritis is the most common disease among Korean. The demand for the development of gastritis drugs has been increasing. Currently, however, there is no guideline available for the clinical evaluation of gastritis drugs worldwide. As a consequence, domestic and international pharmaceutical companies make errors in the drug development processes, and it becomes difficult for them to establish the scientific validity and objectivity of newly developed drugs. The objective of this study was to develop the Guideline for Clinical Trials Evaluation of Gastritis which can be used in improving the quality and consistency of clinical trials. First, we collected and reviewed the clinical trials on gastritis drugs that were available from Japan Pharmaceuticals and Medical Devices Agency and Korea Food and Drug Administration (KFDA), and investigated the recent research trends on clinical trials of gastritis drugs. Reviewers from KFDA and National Institute of Food and Drug Safety Evaluation and scientific experts from the pharmaceutical industries developed the guidelines through regularly scheduled meetings. Opinions and consultation from academic fields and industry experts were also obtained. This project will provide the clinical trial practitioners, investigator and reviewers the scientific and rational guidelines for performance and evaluation of clinical trials for gastritis drugs. Furthermore, we hope this guideline contributes to establishing the national competitiveness, improving the quality of clinical trial, and encouraging researches on drug development for gastritis.