• Title/Summary/Keyword: Drug lead

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The Structure-Activity Relationship of Mansonone F, a Potent Anti-MRSA SesQuiterpenoid Quinone: Insights into Minimum Structural Requirements and SAR of C3 position

  • Jung, Jong-Wha;Shin, Dong-Yun;Chae, Jung-Hyun;Hyun, Soon-Sil;Suh, Young-Ger
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.243.2-244
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    • 2003
  • The resistances to multiple antibiotics of strains of Gram-positive Staphylococci. methicillin-resistant Staphylo coccus aureus (MRSA), are now significant clinical problem. One of the major efforts of our laboratory has been the search and design and synthesis of novel lead compound for the purpose of obtaining highly potent anti-MRSA drug. Towards this end, we have recently reported the isolation of a potent anti-MRSA drug. (omitted)

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Prediction of Childhood Asthma Using Expectation Maximization and Minimum Description Length Algorithm

  • Kim, Hyo Seon;Park, Jong Suk;Nam, Dong Kyu;Jung, Yong Gyu
    • International Journal of Advanced Culture Technology
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    • v.8 no.3
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    • pp.275-279
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    • 2020
  • Due to the recent rapid industrialization worldwide, the number of pediatric asthma patients is increasing. And the fine dust containing heavy metals is linked to the characteristics of high toxic lead due to the increase heating in factory operation and automobile driving. It is the reason of arsenic increasing. In the treatment of pediatric asthma patients, drug administration, oral drug entry, and HMPC (Home Management Plan of Care) are used. In this paper, we analyze the relationship between the onset of asthma and the method of prescription for specific childhood asthma in the United States using EM (Expectation Maximization) and MDL (Minimum Description Length) algorithms. And the association is also analyzed by comparing the nature of specific congestion between the past prevalence of digestive asthma and the recent prevalence of environmental pollution.

Synthesis of Flavokawain B and its Anti-proliferative Activity Against Gefitinib-resistant Non-small Cell Lung Cancer (NSCLC)

  • Seo, Young Ho;Oh, Yong Jin
    • Bulletin of the Korean Chemical Society
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    • v.34 no.12
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    • pp.3782-3786
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    • 2013
  • Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and that accounts for 85% of lung cancer patients. Although several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of EGFR-targeted drugs in NSCLC is limited by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancer due to its potential to simultaneously disable multiple signaling pathways. In this study, we discovered that a natural product, flavokawain B disrupted Hsp90 chaperoning function and impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975). The result suggested that flavokawain B could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

Chao Medicine Treatment Combining Pattern Manifestation(Constitutional Identification, Disease Identification) with Pattern Identification (조의(朝醫) 변상(辨象)(변체질(辨體質), 변병(辨病))과 변증(辨證)을 결합한 치료)

  • Cui, Zhengzhi;Cui, Xingxie
    • Korean Journal of Oriental Medicine
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    • v.14 no.2
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    • pp.155-163
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    • 2008
  • State Administration of Traditional Chinese Medicine of the People's Republic of China lead Research on Chao medicine's Constitutional Treatment project by which could involve the following principles. First, constitution can be identified, second, constitution correlates to ones susceptibility to diseases, third, constitution can be harmonized, fourth, prescription made according to ones constitution and patterns. These ideas is originated by Lee Je-ma's theory of Four Constitution Type in "DongEuiSooSeBoWon"(Longetivity and Life Preservation in Eastern Medicine). This is much similar to currents trends of personalized medicine in western medical sciences. Therefore further developing Lee's theory would have significant value on various fields of medicine.

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Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

  • Choi, Joon-Seok;Joo, Sang Hoon
    • Biomolecules & Therapeutics
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    • v.28 no.1
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    • pp.18-24
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    • 2020
  • Notable progress has been made in the therapeutic and research applications of cyclic peptides since our previous review. New drugs based on cyclic peptides are entering the market, such as plecanatide, a cyclic peptide approved by the United States Food and Drug Administration in 2017 for the treatment of chronic idiopathic constipation. In this review, we discuss recent developments in stapled peptides, prepared with the use of chemical linkers, and bicyclic/tricyclic peptides with more than two rings. These have widespread applications for clinical and research purposes: imaging, diagnostics, improvement of oral absorption, enzyme inhibition, development of receptor agonist/antagonist, and the modulation of protein-protein interaction or protein-RNA interaction. Many cyclic peptides are expected to emerge as therapeutics and biochemical tools.

Synthesis of Butein Analogues and their Anti-proliferative Activity Against Gefitinib-resistant Non-small Cell Lung Cancer (NSCLC) through Hsp90 Inhibition

  • Seo, Young Ho;Jeong, Ju Hui
    • Bulletin of the Korean Chemical Society
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    • v.35 no.5
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    • pp.1294-1298
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    • 2014
  • Non-small cell lung cancer (NSCLC) is the most common type of lung cancer representing 85% of lung cancer patients. Despite several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of these EGFR-targeted therapies is being challenged by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancerous diseases due to its role in modulating and stabilizing numerous oncogenic proteins. Accordingly, inhibition of single Hsp90 protein simultaneously disables multiple signaling networks so as to overcome drug resistance in cancer. In this study, we synthesized a series of 11 butein analogues and evaluated their biological activities against gefitinibresistant NSCLC cells (H1975). Our study indicated that analogue 1h inhibited the proliferation of H1975 cells, down-regulated the expression of Hsp90 client proteins, including EGFR, Met, Her2, Akt and Cdk4, and upregulated the expression of Hsp70. The result suggested that compound 1h disrupted Hsp90 chaperoning function and could serve a potential lead compound to overcome the drug resistance in cancer chemotherapy.

TROGLITAZONE, A NOVEL ANTIDIABETIC DRUG -NEW AVENUE FOR TREATING INSULIN RESISTANCE-

  • Horikoshi, Hiroyoshi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.05a
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    • pp.1-4
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    • 1998
  • Impaired insulin action in Type 2 diabetes is thought to lead to hyperglycemia, with both environmental and complex genetic factors playing key roles. Although the primary lesion in Type 2 diabetes is unknown, a number of studies suggest that metabolic defects in the liver, skeletal muscle and fat, and pancreatic ${\beta}$-cells contribute to the disease. These metabolic abnormalities are characterized by the overproduction of hepatic glucose, impaired insulin secretion, and peripheral insulin resistance. In current pharmacological treatment of Type 2 diabetes, sulfonylurea (SU) drugs have mainly been used as oral hypoglycemic drugs to stimulate endogenous insulin secretion from ${\beta}$ cells. SU drugs, however, sometimes aggravate the disease by causing fatigue of the pancreatic ${\beta}$ cells, which leads to reduced drug efficacy after long-term treatment. This class of drugs also leads to enhanced obesity arising from the stimulation of endogenous insulin secretion in obese Type 2 diabetic patients, plus an increased incidence of SU-induced hypoglycemia. Since 1980, a major challenge has been made by us to develop a potential pharmacological therapy for the treatment of insulin resistance in peripheral tissues and/or suppression of abnormal hepatic glucose production in Type 2 diabetic patients. Such a drug would be expected to have fewer side effects and retain long-term efficacy.

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A Study on Rebates in the Pharmaceutical Industry from the Perspective of New Institutionalism (의약품 리베이트의 원인과 처방에 관한 신제도론적 해석)

  • Lee, Ha-Young;Kwon, Yong-Jin
    • Health Policy and Management
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    • v.21 no.1
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    • pp.132-157
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    • 2011
  • The purpose of this article is to examine the cause of policy non-compliance in the case of pharmaceutical rebates from the perspective of rational choice institutionalism. In Korea, there have been rebates practices between pharmaceutical companies and hospitals since the introduction of the Actual Remuneration System for insured medicine in 1999. The government has chosen the policy means of punishment to eliminate pharmaceutical rebates but the illegal practices are still widespread. Institution in rational choice institutionalism usually reflects the incentives and preferences of actors, and the Actual Remuneration System has resulted in a the lack of procedures to ensure savings on drug expenditures. Pharmaceutical rebates are the product of the institutions which reflect their incentives: the Actual Remuneration System, the current pricing policy for generic drugs, the drug distribution system, and so on. In the end, the problem of the rebates is the consequence of policy non-compliance as actors' rational choice because their incentives lead to opportunistic behaviors. We should therefore understand the incentive structure of policy stakeholders, which is derived from the view of new institutionalism; also, the newly designed Korean drug pricing policy reform must be compatible with the incentive structure.

Antinociceptive and Antiinflammatory Effect of a Diterpene Isolated from the Aerial Part of Siegesbeckia pubescens

  • Park, Hee-Juhn
    • Korean Journal of Plant Resources
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    • v.19 no.6
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    • pp.660-664
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    • 2006
  • The aerial part of Siegesbeckia pubescens (Compositae) has been used to treat rheumatoid arthritis and hypertension in the Oriental medicine. This crude drug has been used without process (SP-0) or with three times-process of steaming and drying (SP-3) or the nine times of that process (SP-9). To search for the antinociceptive anti-inflammatory components from this crude drug, activity-directed fractionation was performed on this crude drug. Since the $CHCl_3$ extract was shown to have a more potent effect than other extracts, it was subjected to silica gel & ODS column chromatography to yield two diterpene compounds (1). Compound 1 was structurally identified as ent-16 (H, 17-hydroxykauran-19-oic acid, which were tentatively named siegeskaurolic acid A. A main diterpene, siegeskaurolic acid A was tested for the antiiflammatory antinociceptive effects using both hot plate- and writhing anti-nociceptive assays and carrageenan-induced anti-inflammatory assays in mice and rats. Pretreatment with siegeskaurolic acid A (20 and 30mg/kg) significantly reduced the stretching episodes, action time of mice and carrageenan-induced edema. These results support that siegeskaurolic acid is a main diterpene responsible for antinociceptive and antiiflammatory action of S. pubescens. In addition, the assays on SP-0, SP-3 and SP-9 produced the experimental results that SP-9 had more significant effects than other two crude drugs. These results suggest that the processing on the original plant may lead to the higher pharmacological effect.

QT-interval prolongation due to medication found in the preoperative evaluation

  • Seto, Mika;Koga, Sayo;Kita, Ryosuke;Kikuta, Toshihiro
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.17 no.4
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    • pp.323-327
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    • 2017
  • QT prolongation is an electrocardiographic change that can lead to lethal arrhythmia. Acquired QT prolongation is known to be caused by drugs and electrolyte abnormalities. We report three cases in which the prolonged QT interval was improved at the time of operation by briefly discontinuing the drugs suspected to have caused the QT prolongation observed on preoperative electrocardiography. The QTc of cases 1, 2, and 3 improved from 518 to 429 ms, 463 to 441 ms, and 473 to 443 ms on discontinuing the use of a gastrointestinal prokinetic agent, a proton pump inhibitor, and a molecular targeted drug, respectively. These cases were considered to have drug-induced QT prolongation. We reaffirmed that even drugs administered for conditions unrelated to cardiac diseases can have adverse side effect of QT prolongation. In conclusion, our cases indicate that dental surgeons should be aware of the dangerous and even potentially lethal side effects of QT prolongation. For safe oral and maxillofacial surgery, cooperation with medical departments in various fields is important.