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Kim S.,Hyundai Pharmaceutical Co. | Kim D.H.,Hyundai Pharmaceutical Co. | Kim D.H.,Chonnam National University | Kim Y.-S.,Hyundai Pharmaceutical Co. | And 5 more authors.
Biomolecules and Therapeutics | Year: 2014

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic β-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent. © 2014 The Korean Society of Applied Pharmacology.


Kim S.R.,Hyundai Pharmaceutical Co. | Kim D.-H.,Hyundai Pharmaceutical Co. | Kim D.-H.,Chonnam National University | Park S.H.,Chonnam National University | And 5 more authors.
Journal of Diabetes Research | Year: 2013

G-protein coupled receptor 119 (GPR119) has emerged as a promising new target for the treatment of type 2 diabetes mellitus. The expression of GPR119 on the pancreatic B cells and intestinal L cells provides a unique opportunity for a single drug to promote insulin and GLP-1 secretion. In this study, we identified a novel small molecule GPR119 agonist, HD0471953, from our large library of synthetic compounds based on its ability to anti-hyperglycemic effects on T2DM murine models. We have tested the acute efficacy of HD0471953 by the oral glucose tolerance test (OGTT) with normal C57BL/6J mice. Then, chronic administrations of HD0471953 were performed to evaluate the efficacy on various diabetic rodent models. Single administration of HD0471953 showed improved glycemic control with a dose-dependent manner in OGTT with normal mice, and the insulin and GLP-1 were also increased. To identify chronic efficacy, we have observed a decline of blood glucose and fasting insulin in a dose-dependent manner of 10, 20, and 50 mpk in db/db mice. The results suggest that HD0471953 may be a potentially promising anti-hyperglycemic agent for the treatment of patients with type 2 diabetes mellitus. © 2013 So Ra Kim et al.


Ha T.-Y.,Hyundai Pharmaceutical Co. | Kim Y.-S.,Hyundai Pharmaceutical Co. | Kim C.H.,Hyundai Pharmaceutical Co. | Choi H.-S.,Hyundai Pharmaceutical Co. | And 4 more authors.
Archives of Pharmacal Research | Year: 2014

In type 2 diabetes mellitus (T2DM) patients, the gradual loss of pancreatic β-cell function is a characteristic feature of disease progression that is associated with sustained hyperglycemia. Recently, G protein-coupled receptor 119 (GPR119) has been identified as a promising anti-diabetic therapeutic target. It is predominantly expressed in pancreatic β-cells, directly promotes glucose stimulated insulin secretion and indirectly increases glucagon-like peptide 1 (GLP-1) levels reducing appetite and food intake. Activation of GPR119 leads to insulin release in β-cells by increasing intracellular cAMP. Here, we identified a novel structural class of small-molecule GPR119 agonists, HD0471042, consisting of substituted a 3-isopropyl-1,2,4-oxadiazol-piperidine derivative with promising potential for the treatment of T2DM. The GPR119 agonist, HD0471042 increased intracellular cAMP levels in stably human GPR119 expressing CHO cell lines and HIT-T15 cell lines, hamster β-cell line expressing endogenously GPR119. HD0471042, significantly elevated insulin release in INS-1 cells of rat pancreatic β-cell line. In in vivo experiments, a single dose of HD0471042 improved glucose tolerance. Insulin and GLP-1 level were increased in a dose-dependent manner. Treatment with HD0471042 for 6 weeks in diet induced obesity mice and for 4 weeks in ob/ob and db/db mice improved glycemic control and also reduced weight gain in a dose-dependent manner. These data demonstrate that the novel GPR119 agonist, HD0471042, not only effectively controlled glucose levels, but also had an anti-obesity effect, a feature observed with GLP-1. We therefore suggest that HD0471042 represents a new type of anti-diabetes agent with anti-obesity potential for the effective treatment of type 2 diabetes. © 2013 The Pharmaceutical Society of Korea.


PubMed | Chonnam National University and Hyundai Pharmaceutical Co.
Type: | Journal: Journal of diabetes research | Year: 2014

G-protein coupled receptor 119 (GPR119) has emerged as a promising new target for the treatment of type 2 diabetes mellitus. The expression of GPR119 on the pancreatic B cells and intestinal L cells provides a unique opportunity for a single drug to promote insulin and GLP-1 secretion. In this study, we identified a novel small molecule GPR119 agonist, HD0471953, from our large library of synthetic compounds based on its ability to anti-hyperglycemic effects on T2DM murine models. We have tested the acute efficacy of HD0471953 by the oral glucose tolerance test (OGTT) with normal C57BL/6J mice. Then, chronic administrations of HD0471953 were performed to evaluate the efficacy on various diabetic rodent models. Single administration of HD0471953 showed improved glycemic control with a dose-dependent manner in OGTT with normal mice, and the insulin and GLP-1 were also increased. To identify chronic efficacy, we have observed a decline of blood glucose and fasting insulin in a dose-dependent manner of 10, 20, and 50 mpk in db/db mice. The results suggest that HD0471953 may be a potentially promising anti-hyperglycemic agent for the treatment of patients with type 2 diabetes mellitus.


PubMed | Chonnam National University, Gachon University and Hyundai Pharmaceutical Co.
Type: Journal Article | Journal: Biomolecules & therapeutics | Year: 2014

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic -cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic -cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.


PubMed | Yonsei University, REPUBLIC RESOURCES and Hyundai Pharmaceutical Co.
Type: | Journal: BioMed research international | Year: 2016

Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity.


News Article | November 30, 2016
Site: www.newsmaker.com.au

The report provides comprehensive information on the therapeutics under development for Cough, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in therapeutic development for Cough   and features dormant and discontinued projects. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Complete report on Cough - Pipeline Review, H2 2016 addition with 38 market data tables and 12 figures, spread across 96 pages is available at http://www.reportsnreports.com/reports/703640-cough-pipeline-review-h2-2016.html This report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Directs proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, Investor presentations and featured press releases from company/university sites and industry-specific third party sources. Drug profiles featured in the report undergoes periodic review following a stringent set of processes to ensure that all the profiles are updated with the latest set of information. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis Ax-8, benzonatate, CCP-05, CCP-06, CCP-07, CCP-08, CLAT-313, codeine + guaifenesin, cromolyn sodium,         DWJ-1340, GRC-17536, GSK-2339345, guaifenesin + hydrocodone, guaifenesin ER , JNJ-39729209, lesogaberan, levodropropizine CR, MD-990, MK-7264, NEO-5937, orvepitant maleate, S-1226, Small Molecule to Antagonize TRPA-1 for Pain And Respiratory Disorders, Small Molecules to Agonize CB1 and CB2 for Chronic Cough and Inflammatory Skin Diseases, ST-015, XEND-0501, Afferent Pharmaceuticals, Alitair Pharmaceuticals, Alveonix AG, AstraZeneca Plc, AusBio Ltd, Charleston Laboratories, Conrig Pharma ApS, Daewoong Pharmaceutical Co., GlaxoSmithKline Plc, Glenmark Pharmaceuticals Ltd., GW Pharmaceuticals Plc, Hyundai Pharmaceutical Co., Johnson & Johnson, NeRRe Therapeutics Ltd, Orbis Biosciences Inc, Inquire before buying http://www.reportsnreports.com/contacts/inquirybeforebuy.aspx?name=703640premium report price at US$2000 for a single user PDF license).


News Article | November 30, 2016
Site: www.newsmaker.com.au

MarketStudyReport.com adds “Global Plasminogen Market Research Report 2016” new report to its research database. The report spread across 106 pages with table and figures in it. This report studies Plasminogen in Global market, especially in North America, Europe, China, Japan, Southeast Asia and India, focuses on top manufacturers in global market, with capacity, production, price, revenue and market share for each manufacturer, covering Browse full table of contents and data tables at https://www.marketstudyreport.com/reports/global-plasminogen-market-research-report-2016/ Market Segment by Regions, this report splits Global into several key Regions, with production, consumption, revenue, market share and growth rate of Plasminogen in these regions, from 2011 to 2021 (forecast), like Split by product type, with production, revenue, price, market share and growth rate of each type, can be divided into Split by application, this report focuses on consumption, market share and growth rate of Plasminogen in each application, can be divided into 7 Global Plasminogen Manufacturers Profiles/Analysis 7.1 Bharat Biotech International Limited 7.1.1 Company Basic Information, Manufacturing Base and Its Competitors 7.1.2 Plasminogen Product Type, Application and Specification 7.1.2.1 Type I 7.1.2.2 Type II 7.1.3 Bharat Biotech International Limited Plasminogen Capacity, Production, Revenue, Price and Gross Margin (2015 and 2016) 7.1.4 Main Business/Business Overview 7.2 F. Hoffmann-La Roche Ltd. 7.2.1 Company Basic Information, Manufacturing Base and Its Competitors 7.2.2 Plasminogen Product Type, Application and Specification 7.2.2.1 Type I 7.2.2.2 Type II 7.2.3 F. Hoffmann-La Roche Ltd. Plasminogen Capacity, Production, Revenue, Price and Gross Margin (2015 and 2016) 7.2.4 Main Business/Business Overview 7.3 Grifols, S.A. 7.3.1 Company Basic Information, Manufacturing Base and Its Competitors 7.3.2 Plasminogen Product Type, Application and Specification 7.3.2.1 Type I 7.3.2.2 Type II 7.3.3 Grifols, S.A. Plasminogen Capacity, Production, Revenue, Price and Gross Margin (2015 and 2016) 7.3.4 Main Business/Business Overview 7.4 Hyundai Pharmaceutical Co., Ltd. 7.4.1 Company Basic Information, Manufacturing Base and Its Competitors 7.4.2 Plasminogen Product Type, Application and Specification 7.4.2.1 Type I 7.4.2.2 Type II 7.4.3 Hyundai Pharmaceutical Co., Ltd. Plasminogen Capacity, Production, Revenue, Price and Gross Margin (2015 and 2016) 7.4.4 Main Business/Business Overview 7.5 Kedrion S.p.A. 7.5.1 Company Basic Information, Manufacturing Base and Its Competitors 7.5.2 Plasminogen Product Type, Application and Specification 7.5.2.1 Type I 7.5.2.2 Type II 7.5.3 Kedrion S.p.A. Plasminogen Capacity, Production, Revenue, Price and Gross Margin (2015 and 2016) 7.5.4 Main Business/Business Overview 7.6 Nostrum Pharmaceuticals, LLC 7.6.1 Company Basic Information, Manufacturing Base and Its Competitors 7.6.2 Plasminogen Product Type, Application and Specification 7.6.2.1 Type I 7.6.2.2 Type II 7.6.3 Nostrum Pharmaceuticals, LLC Plasminogen Capacity, Production, Revenue, Price and Gross Margin (2015 and 2016) 7.6.4 Main Business/Business Overview To receive personalized assistance write to us @ [email protected] with the report title in the subject line along with your questions or call us at +1 866-764-2150


Kim D.H.,Hyundai Pharmaceutical Co. | Lee S.,Chuncheon Bioindustry Foundation | Chung Y.W.,Yonsei University | Kim B.M.,Yonsei University | And 3 more authors.
BioMed Research International | Year: 2016

Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. Copyright © 2016 Dae Hoon Kim et al.

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