• Title/Summary/Keyword: new drug leads

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Synthesis and hypoglycemic Activity of the Substituted Pyrrolidine Thiazolidinedione Derivatives

  • Kim, Bok-Young;Ahn, Joong-Bok;Lee, Hong-Woo;Shin, Jae-Soo;Moon, Kyoung-Sik;Kim, Joon-Kyum;Lee, Do-Young;Ahn, Soon-Kil;Hong, Chung-Il
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.342.3-343
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    • 2002
  • Non-insulin dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia, hyperinsulinemia. and impaired insulin action. Insulin resistance is considered to be the underlying mechanism in the pathogenesis of type 2 diabetes. which also leads to dyslipidemia, hypertension. and obesity. Thazolidinediones are a class of oral insulin-sensitizing agents that improve glucose utilization without increasing insulin release. They significantly reduce glucose, lipid and insulin levels in rodent models of NIDDM and obesity, and recent clinical data support theri efficacy in obese diabetic patients. (omitted)

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Rapid Analysis of Metabolic Stability and Structure of Metabolites in New Drug Development

  • Kim, Dong-Hyun
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.86-87
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    • 2002
  • Recent technological innovations in the drug discovery process such as combinatorial synthesis and high throughput screening have led to the identification of an increasingly large number of compounds at the hits-to-leads stage. Therefore, rapid and precise pharmacokinetic/metabolic screening is essential to enhance the tractability of selected leads and to minimize the risk of failure in the later stages of drug development. (omitted)

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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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Identification of Selective STAT1 Inhibitors by Computational Approach

  • Veena Jaganivasan;Dona Samuel Karen;Bavya Chandrasekhar
    • Journal of Integrative Natural Science
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    • v.16 no.3
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    • pp.81-95
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    • 2023
  • Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

Current status of natural product industry and its commercial application to health functional foods

  • Park, Jong Dae
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.21-21
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    • 2018
  • Natural product substances have historically served as the most significant also be prepared by source of new leads for pharmaceutical development. They can chemical synthesis(both semisynthesis and total synthesis) and have played a important role in the field of organic chemistry by providing synthetic targets. Rcently, they have also been extended for commercial purpose to refer to medicinal products, health functional foods, dietary supplements and cosmetics from natural sources. A large number of currently prescribed drugs have been either directly derived from or inspired by natural products. However, with the advent of robotics, bioinformatics, high throughput screening(HTS), molecular biology-biotechnology, combinatorial chemistry, in silico(molecular modeling) and other methodologies, the pharmaceutical industry has largely moved away from plant derived natural products as a source for leads and prospective drug candidates. The strategy for natural prduct industry is now changing from drug approaches to health foods by identifying effective natural products as preparations. In Korea, a lot of development of natural product based drugs have been done, but very few on health functional foods. The concept of natural product based health foods is not active components as lead compounds but standardized extracts or preparation mixed with other medicinal plants. The representative material has been recently known to be a standardized ginseng extract "Ginsana G 115" developed by Swiss Pharmaton company. The purpose of this presentation is to underline how natural products research continues to make significant contributions in the domain of discovery and development of new health functional foods. It is proposed to present the development of high value added health food or health functional foods through scientific investigation on efficacy and standardization of new materials form natural products.

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Proliferation of Splenocytes and Bone-marrow Cells by Phellinus linteus polysaccharide

  • Joo, Seong-Soo;Kim, Min-Soo;Lee, Do-Ik
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.201-201
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    • 2003
  • The effect of radio- and chemotherapy for cancer are excellent, but their toxicities to normal tissue and organ of the body is relatively strong, which leads secondary side effect to patients during therapies. Particularly, due to the response for bone marrow suppression such as agranulocytosis limits the therapy periods and dose of drugs, new drug development that reproduces lymphocytes has been focused. (omitted)

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Bioactive Constituents of Marine Sponges of the Genus Spongosorites

  • Bao, Baoquan;Hong, Jongki;Lee, Chong-O.;Cho, Hee Young;Jung, Jee H.
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.3
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    • pp.144-155
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    • 2006
  • This report reviews the literatures on chemical constituents of marine sponges of the genus Spongosorites and also highlights our own research. Specific biological activities of the metabolites from these sponges include: cytotoxic, antitumor, antibacterial, antifungal, antiviral, anti-inflammatory, and other pharmacological activities.

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GEDA: New Knowledge Base of Gene Expression in Drug Addiction

  • Suh, Young-Ju;Yang, Moon-Hee;Yoon, Suk-Joon;Park, Jong-Hoon
    • BMB Reports
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    • v.39 no.4
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    • pp.441-447
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    • 2006
  • Abuse of drugs can elicit compulsive drug seeking behaviors upon repeated administration, and ultimately leads to the phenomenon of addiction. We developed a procedure for the standardization of microarray gene expression data of rat brain in drug addiction and stored them in a single integrated database system, focusing on more effective data processing and interpretation. Another characteristic of the present database is that it has a systematic flexibility for statistical analysis and linking with other databases. Basically, we adopt an intelligent SQL querying system, as the foundation of our DB, in order to set up an interactive module which can automatically read the raw gene expression data in the standardized format. We maximize the usability of this DB, helping users study significant gene expression and identify biological function of the genes through integrated up-to-date gene information such as GO annotation and metabolic pathway. For collecting the latest information of selected gene from the database, we also set up the local BLAST search engine and non-redundant sequence database updated by NCBI server on a daily basis. We find that the present database is a useful query interface and data-mining tool, specifically for finding out the genes related to drug addiction. We apply this system to the identification and characterization of methamphetamine-induced genes' behavior in rat brain.

Synthesis and Bioactivity of Quercetin Aspirinates

  • Lu, Chenjuan;Huang, Feng;Li, Zexin;Ma, Jinshuo;Li, Huanhuan;Fang, Lizhen
    • Bulletin of the Korean Chemical Society
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    • v.35 no.2
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    • pp.518-520
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    • 2014
  • Hybrids of some natural compounds are promising to obtain new leads with good biological activities for drug discovery. Three quercetin aspirinates were synthesized by esterification of the 3-and 7-hydroxyl groups of quercetin with aspirin. Biological activities of these quercetin aspirinates were initially screened and showed better cytotoxic activities against tumor cell lines HL-60 and HepG2 and less scavenging activity against DPPH than the quercetin respectively.