• 한국환경독성학회:학술대회논문집
• /
• 한국환경독성학회 2002년도 추계국제학술대회
• /
• pp.173-173
• /
• 2002

In order to understand the mechanism of action of TCDD, we have examined the effect of COX-inhibitors on cyp1a1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cyp1a1 mRNA, mouse cyp1a1 promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. And Pretreatment of Aspirin, Celecoxib, Nimesulide and other several Cox-inhibitors in vitro, inhibited the TCDD stimulated EROD activity and Luciferase acitivity. In case of cyp1a1 mRNA level, Nimesulide and SB100 were able to decrease cyp1a1 mRNA that was stimulated by TCDD, but other tested COX-inhibitors were not decrease. We don't know this different result exactly. For the action of Cox-inhibitors on the Cyp1a1, it seems to be important to do pretreatment of these chemicals as apposed to TCDD. In this study, thus, we have suggested that COX-inhibitors such as aspirin, celecoxib, Nimesulide and other several Cox-inhibitors decrease the TCDD induced Cyp1a1.

• 한국임상약학회지
• /
• 제23권2호
• /
• pp.129-136
• /
• 2013

Objectives: Among many new drugs that are under investigation with intent to treat cancer, oral kinase inhibitors are proven to be effective in numerous clinical trials and easy to administer. Due to these advantages the use of oral kinase inhibitors is increasing. Oral kinase inhibitors are metabolized by CYP450 which can result either increase of adverse effect or decrease of drug effect by drug interaction when used concurrently with other agents. In this research, the medication records of patients on oral kinase inhibitors from Oct. 2010 to Nov. 2011 were reviewed to investigate potential drug interactions. Methods: From Oct. 2010 to Nov. 2011, cancer patients in Inha University Hospital who took oral kinase inhibitors more than once were included. The patients' medication records were reviewed to list out concurrent medications that have interaction potential with oral kinase inhibitors, the frequency of concurrent use, and the severity of interaction result using Micromedex$^{(R)}$ and Lexicomp-online$^{(R)}$ as references. Results: As a result, 90 cases of drug with interaction potential were prescribed by Micromedex$^{(R)}$ and 179 cases by Lexicomp-online$^{(R)}$ data. In case of severity, 33.3% by Micromedex$^{(R)}$ and 26.3% by Lexicomp-online$^{(R)}$ were categorized as Major and 65.6% by Micromedex$^{(R)}$ and 72.6% by Lexicomp-online$^{(R)}$ as Moderate. The number of adverse events was 92 cases which 58.7% were on skin and 19.6% on Gastro-intestinal tract. Conclusions: Considerable number of drug with interaction potential was used though each oral kinase inhibitors showed differences in extent. Hence there exists the risk of drug interaction in patients taking oral kinase inhibitors with other drugs.

• 한국식품과학회지
• /
• 제14권2호
• /
• pp.106-111
• /
• 1982

대두 7품종과 이를 이면교잡(二面交雜)해서 얻은 2대 21종의 대두에서 각각 가용성 단백질을 추출하여 Sephadex G-75에 의한 겔 여과와 polyacrylamide 겔 전기영동으로 트립신 인히비터를 분획 정제한 결과 16종의 트립신 인히비터가 검출되었고 각종류의 대두마다 $5{\sim}12$종의 트립신 인히비터가 존재하였으며 주로 5종의 트립신 인히비터가 분포하였다.

• Tuberculosis and Respiratory Diseases
• /
• 제75권5호
• /
• pp.188-198
• /
• 2013

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

• Biomolecules & Therapeutics
• /
• 제9권2호
• /
• pp.69-78
• /
• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• Bulletin of the Korean Chemical Society
• /
• 제3권3호
• /
• pp.122-129
• /
• 1982

In order to extend our understanding on the multiple inhibition enzyme kinetics, a general equation of an enzyme reaction in the presence of two different reversible inhibitors was derived by what we call "match-box mechanism" under the combined assumption of steady-state and quasi-equilibrium for inhibitor binding. Graphical methods were proposed to analyze the multiple inhibition of an enzyme by any given sets of different inhibitors, i.e., competitive, noncompetitive, and uncompetitive inhibitors. This method not only gives an interaction factor $({\alpha})$ between two inhibitors, but also discerns ${\alpha}_1$ and ${\alpha}_2$ with and without substrate binding, respectively. The factors involved in the dissociation constants of inhibitors can also be evaluated by the present plot. It is also shown that the present kinetic approach can be extended to other forms of activators or hydrogen ions with some modification.

• Bulletin of the Korean Chemical Society
• /
• 제21권11호
• /
• pp.1085-1089
• /
• 2000

The effect of 2-hydroxyacetophenone-aroyl hydrazone derivatives on the inhibition of copper corrosion in 3N nitric acid solution at 303 K was investigated by galvanostatic polarization and thermometric techniques. A significant decrease in the cor rosion rate of copper was observed in the presence of the investigated compounds. The corrosion rate was found to depend on the nature and concentrations of the inhibitors. The degree of surface coverage of the adsorbed inhibitors is determined from polarization measurements, and it was found that the results obey the Frumkin adsorption isotherm. The inhibitors acted as mixed-type inhibitors, but the cathode is more polarized. The relative inhibitive efficiency of these compounds has been explained on the basis of structure dependent electron donor properties of the inhibitors and the nature of the metal-inhibitor interaction at the surface. Also, some thermodynamic data for the adsorption process ( ΔGa* and f ) are calculated and discussed.

• Interdisciplinary Bio Central
• /
• 제4권1호
• /
• pp.2.1-2.7
• /
• 2012

Introduction: Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from ${\varepsilon}$-N-acetyl lysine amino acids of histone proteins. Their action is opposite to that of histone acetyltransferase that adds acetyl groups to these lysines. Only few HDAC inhibitors are approved and used as anti-cancer therapeutics. Thus, discovery of new and potential HDAC inhibitors are necessary in the effective treatment of cancer. Materials and Methods: This study proposed a method using support vector machine (SVM) to classify HDAC8 inhibitors and non-inhibitors in early-phase virtual compound filtering and screening. The 100 experimentally known HDAC8 inhibitors including 52 inhibitors and 48 non-inhibitors were used in this study. A set of molecular descriptors was calculated for all compounds in the dataset using ADRIANA. Code of Molecular Networks. Different kernel functions available from SVM Tools of free support vector machine software and training and test sets of varying size were used in model generation and validation. Results and Conclusion: The best model obtained using kernel functions has shown 75% of accuracy on test set prediction. The other models have also displayed good prediction over the test set compounds. The results of this study can be used as simple and effective filters in the drug discovery process.

• Biomolecules & Therapeutics
• /
• 제20권1호
• /
• pp.81-88
• /
• 2012

Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identifi ed and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at $G_2$/M phase. At the same time, IN-2001 treatment time-dependently increased sub-$G_1$ population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased $p21^{WAF1}$ and $p27^{KIP1}$ expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.

• 한국임상약학회지
• /
• 제31권3호
• /
• pp.188-197
• /
• 2021

Objective: PD-1 inhibitors have demonstrated improved health outcomes in cancer patients. PD-1 inhibitors are well-tolerated and associated with immune-related adverse events. The objectives of this study are to analyze use patterns of PD-1 inhibitors in patients with cancer and to investigate the incidence of thyroid-related adverse reactions in patients treated with PD-1 inhibitors. Methods: The study included patients who had been administered PD-1 inhibitors (either nivolumab or pembrolizumab) at the Samsung Medical Center between October 1, 2016 and June 30, 2017. Data was collected from electronic medical records and tested using Mann-Whitney tests and Chi-Square tests for statistical significance. Associations between PD-1 inhibitors and incidence of adverse events were tested using Cox regression for age, gender, BMI, ECOG PS and medication. Results: Two hundred fifteen patients were identified as eligible for analyses. Thyroid-related adverse events occurred in 20% of patients (n=43). Thyroid function tests (TFTs) was performed in 109 patients (50.7%). Positive results of PD-L1 testing were found in 53.2% of the 94 patients who had the test. Approved doses of nivolumab (3 m/kg) and pembrolizumab (200 mg) were administered in 70.4% and 53% of patients, respectively. The analysis of risk factor of thyroid-related adverse reaction did not show statistically significant differences (Cox regression). Conclusion: Thyroid-related adverse events are common in patients treated with PD-1 inhibitors and hypothyroidism is the most frequent adverse reaction. Routine TFTs monitoring is strongly recommended to evaluate thyroid function in real-world clinical practice.