Ansan, South Korea
Ansan, South Korea

Time filter

Source Type

Hoang V.-H.,Seoul National University | Tran P.-T.,Seoul National University | Tran P.-T.,Hanoi University of Pharmacy | Cui M.,Ewha Womans University | And 12 more authors.
Journal of Medicinal Chemistry | Year: 2017

Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ3E−42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD. © 2017 American Chemical Society.


News Article | November 29, 2016
Site: www.PR.com

Report provides comprehensive information on the therapeutics under development for Diabetic Neuropathic Pain, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. Albany, NY, November 29, 2016 --( Request for Free Sample Report: http://www.marketresearchhub.com/enquiry.php?type=S&repid=873453 As the name suggests, diabetic neuropathy is a nerve disorder caused by diabetes, also referred as Metabolic Disorder. The longer a person has been diabetic, the danger of diabetic neuropathy increases. This nerve damage can manifest itself anywhere in the body, such as heart, sex organs and the digestive system. The influencing factors are obesity, hypertension, high lipid and sugar levels, smoking etc. It further leads to lack of sensation, tingling in hands, arms and feet. The report estimates that more than 50 percent of people who have diabetes are affected by some type of neuropathy and maximum rates of neuropathy are amongst the public who have had diabetes for close to 25 years. It is not limited only to diabetic patients but it could also affect people who are not able to control their blood pressure or are overweight. People who are above 40 years of age are also affected by neuropathy. The study observes that, diabetic neuropathy can be managed through medication and dietary modification. Pain relieving treatment includes anti-seizure medications such as gabapentin, pregabalin & carbamazepine, anti-depressants medications and capsaicin cream. In addition to this, nitrate sprays or patches for the feet may also relieve pain. The guide also covers the drug profiles used by the companies for the therapy along with the product description, mechanism of action and R&D progress. Additionally, various dynamic tracking processes ensure that the most recent developments are bagged on a real time basis. Companies involved in Therapeutics Development of Diabetic Neuropathy are listed below: Achelios Therapeutics, Inc. KPI Therapeutics, Inc. Araim Pharmaceuticals, Inc. Celgene Corporation Commence Bio, Inc. NovaLead Pharma Pvt. Ltd. Glucox Biotech AB Lpath, Inc. Medifron DBT Co., Ltd. Neuralstem, Inc. Novartis AG Relief Therapeutics S.A. Omeros Corporation PhiloGene, Inc. Reata Pharmaceuticals, Inc. Sucampo Pharmaceuticals, Inc. ViroMed Co Ltd Browse Full Info with TOC: http://www.marketresearchhub.com/report/diabetic-neuropathy-pipeline-review-h2-2016-report.html. Further, the report features investigational drugs from across the globe covering over 20 therapy areas and nearly 3,000 indications. Additionally, report also summarizes all the dormant and discontinued pipeline projects. About Us Market Research Hub (MRH) is a next-generation reseller of research reports and analysis. MRH’s expansive collection of market research reports has been carefully curated to help key personnel and decision makers across industry verticals to clearly visualize their operating environment and take strategic steps. MRH functions as an integrated platform for the following products and services: Objective and sound market forecasts, qualitative and quantitative analysis, incisive insight into defining industry trends, and market share estimates. Our reputation lies in delivering value and world-class capabilities to our clients. Contact Us 90 State Street Albany, NY 12207 United States Toll Free: 866-997-4948 (US-Canada) Tel: +1-518-621-2074 Email: press@marketresearchhub.com Website: http://www.marketresearchhub.com Albany, NY, November 29, 2016 --( PR.com )-- A recent report focusing on the therapeutic development of the disease called “Diabetic Neuropathy” has been added to the massive collection of Market Research Hub’s research reports. It is the latest report by Global Markets Direct, titled as “Diabetic Neuropathy- Pipeline Review, H2 2016.” The report offers therapeutic assessment with comparative analysis at several stages, drug target, route of administration (RoA), mechanism of action (MoA) and molecule type. This guide covers the descriptive pharmacological action of the therapeutics along with its complete research and development history along with latest news & press releases.Request for Free Sample Report: http://www.marketresearchhub.com/enquiry.php?type=S&repid=873453As the name suggests, diabetic neuropathy is a nerve disorder caused by diabetes, also referred as Metabolic Disorder. The longer a person has been diabetic, the danger of diabetic neuropathy increases. This nerve damage can manifest itself anywhere in the body, such as heart, sex organs and the digestive system. The influencing factors are obesity, hypertension, high lipid and sugar levels, smoking etc. It further leads to lack of sensation, tingling in hands, arms and feet. The report estimates that more than 50 percent of people who have diabetes are affected by some type of neuropathy and maximum rates of neuropathy are amongst the public who have had diabetes for close to 25 years. It is not limited only to diabetic patients but it could also affect people who are not able to control their blood pressure or are overweight. People who are above 40 years of age are also affected by neuropathy.The study observes that, diabetic neuropathy can be managed through medication and dietary modification. Pain relieving treatment includes anti-seizure medications such as gabapentin, pregabalin & carbamazepine, anti-depressants medications and capsaicin cream. In addition to this, nitrate sprays or patches for the feet may also relieve pain. The guide also covers the drug profiles used by the companies for the therapy along with the product description, mechanism of action and R&D progress. Additionally, various dynamic tracking processes ensure that the most recent developments are bagged on a real time basis.Companies involved in Therapeutics Development of Diabetic Neuropathy are listed below:Achelios Therapeutics, Inc.KPI Therapeutics, Inc.Araim Pharmaceuticals, Inc.Celgene CorporationCommence Bio, Inc.NovaLead Pharma Pvt. Ltd.Glucox Biotech ABLpath, Inc.Medifron DBT Co., Ltd.Neuralstem, Inc.Novartis AGRelief Therapeutics S.A.Omeros CorporationPhiloGene, Inc.Reata Pharmaceuticals, Inc.Sucampo Pharmaceuticals, Inc.ViroMed Co LtdBrowse Full Info with TOC: http://www.marketresearchhub.com/report/diabetic-neuropathy-pipeline-review-h2-2016-report.html.Further, the report features investigational drugs from across the globe covering over 20 therapy areas and nearly 3,000 indications. Additionally, report also summarizes all the dormant and discontinued pipeline projects.About UsMarket Research Hub (MRH) is a next-generation reseller of research reports and analysis. MRH’s expansive collection of market research reports has been carefully curated to help key personnel and decision makers across industry verticals to clearly visualize their operating environment and take strategic steps.MRH functions as an integrated platform for the following products and services: Objective and sound market forecasts, qualitative and quantitative analysis, incisive insight into defining industry trends, and market share estimates. Our reputation lies in delivering value and world-class capabilities to our clients.Contact Us90 State StreetAlbany, NY 12207United StatesToll Free: 866-997-4948 (US-Canada)Tel: +1-518-621-2074Email: press@marketresearchhub.comWebsite: http://www.marketresearchhub.com Click here to view the list of recent Press Releases from Market Research Hub


Han Y.T.,Woosuk University | Kim K.,Seoul National University | Choi G.-I.,Seoul National University | An H.,Seoul National University | And 8 more authors.
European Journal of Medicinal Chemistry | Year: 2014

In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5- carboxamides. The brain Aβ-lowering effect of 40 is also described. © 2014 Elsevier Masson SAS. All rights reserved.


Han Y.T.,Woosuk University | Kim K.,Seoul National University | Son D.,Sungkyunkwan University | An H.,Seoul National University | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2014

Through the fine tuning of the activity-sensitive aminoalkoxy moiety of 4,6-bisphenyl-2-(3-alkoxyanilino)pyrimidine as a novel inhibitor of the receptor for advanced glycation end products (RAGE), the tertiary amine was elucidated as an essential part associated with RAGE inhibition. On the basis of this finding, a 3-(N,. N-dimethylamino)pyrrolidine analog 12o was identified as a therapeutically useful RAGE inhibitor with improved activity and solubility. Molecular modeling studies predicted that the improved inhibitory activity is induced by additional hydrogen bonds between the nitrogen atom of the pyrrolidine ring and Arg48 and by an interaction between the dimethylamino-substituent of the pyrrolidine moiety and a relatively hydrophobic groove in the RAGE binding site. © 2014 Elsevier Ltd.


Lee S.-C.,Seoul National University | Min H.-Y.,Seoul National University | Choi H.,Seoul National University | Kim H.S.,Seoul National University | And 12 more authors.
Molecular Pharmacology | Year: 2015

The clinical benefit of current anticancer regimens for lung cancer therapy is still limited due to moderate efficacy, drug resistance, and recurrence. Therefore, the development of effective anticancer drugs for first-line therapy and for optimal second-line treatment is necessary. Because the 90-kDa molecular chaperone heat shock protein (Hsp90) contributes to the maturation of numerous mutated or overexpressed oncogenic proteins, targeting Hsp90 may offer an effective anticancer therapy. Here, we investigated antitumor activities and toxicity of a novel deguelin-derived C-terminal Hsp90 inhibitor, designated L80. L80 displayed significant inhibitory effects on the viability, colony formation, angiogenesis-stimulating activity, migration, and invasion of a panel of non-small cell lung cancer cell lines and their sublines with acquired resistance to paclitaxel with minimal toxicity to normal lung epithelial cells, hippocampal cells, vascular endothelial cells, and ocular cells. Biochemical analyses and molecular docking simulation revealed that L80 disrupted Hsp90 function by binding to the C-terminal ATP-binding pocket of Hsp90, leading to the disruption of the interaction between hypoxia-inducible factor (HIF)-1α and Hsp90, downregulation of HIF-1α and its target genes, including vascular endothelial growth factor (VEGF) and insulin-like growth factor 2 (IGF2), and decreased the expression of various Hsp90 client proteins. Consistent with these in vitro findings, L80 exhibited significant antitumor and antiangiogenic activities in H1299 xenograft tumors. These results suggest that L80 represents a novel C-terminal Hsp90 inhibitor with effective anticancer activities with minimal toxicities. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.


Han Y.T.,Seoul National University | Choi G.-I.,Seoul National University | Son D.,Sungkyunkwan University | Kim N.-J.,Seoul National University | And 10 more authors.
Journal of Medicinal Chemistry | Year: 2012

Using the approach of ligand-based drug design, we discovered a novel series of 4,6-disubstituted 2-aminopyrimidines as RAGE inhibitors. In transgenic mouse models of AD, one of the 4,6-bis(4-chlorophenyl)pyrimidine analogs, 59, significantly lowered the concentration of toxic soluble Aβ in the brain and improved cognitive function. SPR analysis confirmed the direct binding of 59 with RAGE, which should contribute to its biological activities via inhibition of the RAGE-Aβ interaction. We also predicted the binding mode of the 4,6-bis(4-chlorophenyl)pyrimidine analogs to the RAGE V-domain through flexible docking study. © 2012 American Chemical Society.


Lee J.,Seoul National University | Choi K.,Seoul National University | Lim K.S.,Seoul National University | Shin J.,Seoul National University | And 7 more authors.
Bioorganic and Medicinal Chemistry | Year: 2015

Receptor for advanced glycation end products (RAGE) is known to be involved in the transportation of amyloid β (Aβ) peptides and causes the accumulation of Aβ in the brain. Moreover, recent studies suggest that the interactions between RAGE and Aβ peptides may be the culprit behind Alzheimer's disease (AD). Inhibitors of the RAGE-Aβ interactions would not only prevent the accumulation of toxic Aβ in the brain, and but also block the progress of AD, therefore, have the potential to provide a 'disease-modifying therapy'. In this study, we have developed a series of 6-phenoxy-2-phenylbenzoxazole analogs as novel inhibitors of RAGE. Among these derivatives, we found several effective inhibitors that block the RAGE-Aβ interactions without causing significant cellular toxicity. Further testing showed that compound 48 suppressed Aβ induced toxicity in mouse hippocampal neuronal cells and reduced Aβ levels in the brains of a transgenic mouse model of AD after oral administration. © 2015 Elsevier Ltd. All rights reserved.


PubMed | University of Seoul, Medifron DBT and Seoul National University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

Receptor for advanced glycation end products (RAGE) is known to be involved in the transportation of amyloid (A) peptides and causes the accumulation of A in the brain. Moreover, recent studies suggest that the interactions between RAGE and A peptides may be the culprit behind Alzheimers disease (AD). Inhibitors of the RAGE-A interactions would not only prevent the accumulation of toxic A in the brain, and but also block the progress of AD, therefore, have the potential to provide a disease-modifying therapy. In this study, we have developed a series of 6-phenoxy-2-phenylbenzoxazole analogs as novel inhibitors of RAGE. Among these derivatives, we found several effective inhibitors that block the RAGE-A interactions without causing significant cellular toxicity. Further testing showed that compound 48 suppressed A induced toxicity in mouse hippocampal neuronal cells and reduced A levels in the brains of a transgenic mouse model of AD after oral administration.


Lee Y.S.,Korea Institute of Science and Technology | Lee Y.S.,Korea University | Kim H.,Medifron DBT | Kim Y.-H.,Medifron DBT | And 3 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

A series of thiazole derivatives were designed, and prepared to develop RAGE antagonist for the treatment of Alzheimer's disease (AD). SAR studies were performed to optimize inhibitory activity on Aβ-RAGE binding. SAR studies showed that introducing an amino group at part A was essential for inhibitory activity on Aβ-RAGE binding. Compounds selected from Aβ-RAGE binding screening displayed inhibitory activity on Aβ transport across BBB. They also showed inhibitory activity against Aβ-induced NF-κB activation. These results indicated that our derivatives had a potential as therapeutic agent for the treatment of AD. © 2012 Elsevier Ltd. All rights reserved.

Loading Medifron DBT collaborators
Loading Medifron DBT collaborators