DOCSLIB.ORG

Diabetes Europe 2018: in Vivo Assessment of Thiazolidinedione Subsidiaries As Euglycemic Specialists- Diana Aleman- National Polytechnic Institute

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Diabetes Europe 2018: in Vivo Assessment of Thiazolidinedione Subsidiaries As Euglycemic Specialists- Diana Aleman- National Polytechnic Institute Extended Abstract Reports in Endocrine Disorders: Open Access Vol. 4, Iss. 1 2020 Diabetes Europe 2018: In vivo assessment of thiazolidinedione subsidiaries as euglycemic specialists- Diana Aleman- National Polytechnic Institute Diana Aleman National Polytechnic Institute, Mexico Introduction: Diabetes Mellitus (DM) is an euglycemia. The three subordinates expanded the incessant metabolic ailment which can be dealt estimations of absolute cholesterol, while with either by diminishing blood glucose by the triglyceride levels diminished. C#4 showed a improvement in insulin discharge or by superior cancer prevention agent action as diminishing insulin obstruction in fringe tissues opposed to C#40, C#81 and Pioglitazone, by which is a trademark impact of expanding Turf, Feline, GSH levels by decreasing Thiazolidinediones (TZDs). TZDs are finished Ski lifts levels. End: C#40 was compelling for the agonists of the Peroxisome Proliferator-Actuated decline of blood glucose and triglycerides. It was (PPAR) γ receptor, which can advance the discovered that C#4 is a powerful cell interpretation of qualities associated with the reinforcement compound, as opposed to C#40, digestion of lipids and sugars, yet these C#81 and Pioglitazone. medications present unwanted impacts, for Diabetes mellitus is a genuine worldwide medical example, increment in body weight, hepatic issue and having its spot as one of the primary harmfulness, plasma volume development and dangers to human wellbeing in the 21st century. cardiovascular breakdown. The point of this The National Diabetes Data Clearinghouse and examination was to clarify whether our recently World Wellbeing Association appears above 90% structured mixes, known as C#40, C#81 and C#4, of the diabetic populace fall under sort 2 diabetes may fill in as euglycemic and cancer prevention mellitus class. The treatment by and large agent specialists. Material and Procedure: Sound endorsed for type 2 diabetes mellitus has been a male Wistar rodents were arbitrarily isolated into blend of diet, exercise and current remedial 6 gatherings, each containing 7 creatures as- specialists Because of their antagonistic impacts Control, DM, DM+Pioglitazone, DM+C#40, and reactions, the greater part of these medicines DM+C#81 and DM+C#4. DM was instigated by a are viewed as unacceptable as far as counteraction solitary intra-peritoneal infusion of streptozotocin of intricacies and protection of personal (45 mg/kg). After the infusion, every creature was satisfaction. The present restorative operators weighted and checked for blood glucose levels containing thiazolidine-2,4-diones or glitazones week by week. Toward the finish of the are indicated better treatment on type 2 diabetes investigation, blood and hepatic tissue tests were mellitus by means of following up on peroxisome gathered so as to decide glucose, insulin, proliferator-enacted receptor-gamma (PPAR-γ). triglycerides, complete cholesterol, cell From these glitazones, troglitazone and reinforcement enzymatic action, cancer prevention rosiglitazone are pulled back from business agent non-enzymatic action and liver proteins. sectors. Pioglitazone and lobeglitazone are Results: The treatment with C#40 had the option utilized in advertise. Ciglitazone, englitazone, to deliver euglycemia better than Pioglitazone, darglitazone, KRP-297, rivoglitazone and CLX- while C#81 had the option to lessen glycemia by 921 are ended in different clinical preliminaries. 300 mg/dl, despite the fact that it didn't create Mitoglitazone, netoglitazone and balaglitazone are Note: This work is partly presented at 14th World Congress on Endocrinology & Diabetes November 21-22, 2018 at Paris, France Extended Abstract Reports in Endocrine Disorders: Open Access Vol. 4, Iss. 1 2020 available in different periods of clinical undesirable symptoms. Future examinations of preliminaries. Besides, in view of different writing pyrazole, chromone, and corrosive put together studies, we are concentrated in subtleties structure TZD framework are justified with respect to other action connections of different glitazones. atomic focuses of TZD, which can give us all the more reassuring outcomes. In view of the accessible investigation results, TZDs can be Presently a day, the overall pervasiveness of considered as one of the promising classes of diabetes mellitus is expanding. Because of intensifies that can conquer issues of the clinically expands the development of populace, maturing, utilized TZDs in the administration of diabetes. urbanization, heftiness and physical stability issues. The for the most part endorsed treatment for diabetes mellitus has been a mix of diet, exercise, and ebb and flow remedial specialists, for example, insulin, sulphonylureas, metformin, acarbose, thiazolidine2,4-diones, glucagon like peptide analogs and dipeptidyl peptidase type-4 inhibitors. From these present restorative specialists, thiazolidine-2,4-diones are expanded insulin affectability activity in fat, muscle and hepatic tissues through following up on PPAR-γ. In the concise conversation of different replacement present at the 5-position of thiazolidine-2,4-diones and its planned SAR considers are reasoned that, adjustment of the effector locale and focal linker district, without change of sweet-smelling ring present at the focal linker area and thiazolidine-2,4-dione ring present at the coupling locale towards the amalgamation and improvement of new thiazolidine-2,4-diones as oral hypoglycemic operators. Alteration of thiazolidinedione have demonstrated exceptionally powerful and made to improve intensity. Lobeglitazone and Mitoglitazone can be used as antidiabetic specialist. In future other thiazolidinedione subordinates and numerous other licensed atoms can likewise be utilized as antidiabetic operators. Additionally, concentrates on different methodologies, for example, virtual screening, in-silico sedate plan, docking and so forth can be used to build up this class medicine for focusing on other sub-atomic focuses of diabetes to maintain a strategic distance from Note: This work is partly presented at 14th World Congress on Endocrinology & Diabetes November 21-22, 2018 at Paris, France .
Load more

Recommended publications
  • The Antidiabetic Drug Lobeglitazone Has the Potential to Inhibit PTP1B T Activity ⁎ Ruth F
    Bioorganic Chemistry 100 (2020) 103927 Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg The antidiabetic drug lobeglitazone has the potential to inhibit PTP1B T activity ⁎ Ruth F. Rochaa, Tiago Rodriguesc, Angela C.O. Menegattia,b, , Gonçalo J.L. Bernardesc,d, Hernán Terenzia a Centro de Biologia Molecular Estrutural, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC, Brazil b Universidade Federal do Piauí, CPCE, 64900-000 Bom Jesus, PI, Brazil c Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal d Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, UK ARTICLE INFO ABSTRACT Keywords: Protein tyrosine phosphatase 1B (PTP1B) is considered a potential therapeutic target for the treatment of type 2 Thiazolidinediones diabetes mellitus (T2DM), since this enzyme plays a significant role to down-regulate insulin and leptin sig- Lobeglitazone nalling and its over expression has been implicated in the development of insulin resistance, T2DM and obesity. PPAR-γ Some thiazolidinediones (TZD) derivatives have been reported as promising PTP1B inhibitors with anti hy- PTP1B perglycemic effects. Recently, lobeglitazone, a new TZD, was described as an antidiabetic drug that targetsthe Non-competitive inhibitors PPAR-γ (peroxisome γ proliferator-activated receptor) pathway, but no information on its effects on PTP1B have been reported to date. We investigated the effects of lobeglitazone on PTP1B activity in vitro. Surprisingly, lobeglitazone led to moderate inhibition on PTP1B (IC50 42.8 ± 3.8 µM) activity and to a non-competitive reversible mechanism of action.
    [Show full text]
  • Dualism of Peroxisome Proliferator-Activated Receptor Α/Γ: a Potent Clincher in Insulin Resistance
    AEGAEUM JOURNAL ISSN NO: 0776-3808 Dualism of Peroxisome Proliferator-Activated Receptor α/γ: A Potent Clincher in Insulin Resistance Mr. Ravikumar R. Thakar1 and Dr. Nilesh J. Patel1* 1Faculty of Pharmacy, Shree S. K. Patel College of Pharmaceutical Education & Research, Ganpat University, Gujarat, India. [email protected] Abstract: Diabetes mellitus is clinical syndrome which is signalised by augmenting level of sugar in blood stream, which produced through lacking of insulin level and defective insulin activity or both. As per worldwide epidemiology data suggested that the numbers of people with T2DM living in developing countries is increasing with 80% of people with T2DM. Peroxisome proliferator-activated receptors are a family of ligand-activated transcription factors; modulate the expression of many genes. PPARs have three isoforms namely PPARα, PPARβ/δ and PPARγ that play a central role in regulating glucose, lipid and cholesterol metabolism where imbalance can lead to obesity, T2DM and CV ailments. It have pathogenic role in diabetes. PPARα is regulates the metabolism of lipids, carbohydrates, and amino acids, activated by ligands such as polyunsaturated fatty acids, and drugs used as Lipid lowering agents. PPAR β/δ could envision as a therapeutic option for the correction of diabetes and a variety of inflammatory conditions. PPARγ is well categorized, an element of the PPARs, also pharmacological effective as an insulin resistance lowering agents, are used as a remedy for insulin resistance integrated with type- 2 diabetes mellitus. There are mechanistic role of PPARα, PPARβ/δ and PPARγ in diabetes mellitus and insulin resistance. From mechanistic way, it revealed that dual PPAR-α/γ agonist play important role in regulating both lipids as well as glycemic levels with essential safety issues.
    [Show full text]
  • Corporate Presentation June 2019 Disclaimer
    Corporate Presentation June 2019 Disclaimer Some of the statements contained in this presentation constitute forward-looking statements. Statements that are not historical facts are forward-looking statements. Forward-looking statements generally can be identified by the use of forward-looking terminology such as “may”, “will”, “expect”, “intend”, “estimate”, “anticipate”, “believe”, “continue” or similar terminology. These statements are based on the Company’s current strategy, plans, objectives, assumptions, estimates and projections. Investors should therefore not place undue reliance on those statements. The Company makes no representation, warranty or prediction that the results anticipated by such forward- looking statements will be achieved, and such forward-looking statements represent, in each case, only one of many possible scenarios and should not be viewed as the most likely or standard scenario. Forward-looking statements speak only as of the date that they are made and the Company does not undertake to update any forward-looking statements in light of new information or future events. Forward-looking statements involve inherent risks and uncertainties. The Company cautions that a number of important factors could cause actual results to differ materially from those contained in any forward-looking statement. 2 Well Diversified Mid-to-Late Stage Metabolic Pipeline for Large Market Opportunities Global partnerships secured for late stage clinical program in type 2 diabetes • Imeglimin: First in class oral drug candidate targeting
    [Show full text]
  • CDR Clinical Review Report for Soliqua
    CADTH COMMON DRUG REVIEW Clinical Review Report Insulin glargine and lixisenatide injection (Soliqua) (Sanofi-Aventis) Indication: adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (less than 60 units daily) alone or in combination with metformin. Service Line: CADTH Common Drug Review Version: Final (with redactions) Publication Date: January 2019 Report Length: 118 Pages Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document.
    [Show full text]
  • Lobeglitazone
    2013 International Conference on Diabetes and Metabolism Lobeglitazone, A Novel PPAR-γ agonist with balanced efficacy and safety Kim, Sin Gon. MD, PhD. Professor, Division of Endocrinology and Metabolism Department of Internal Medicine, Korea University College of Medicine. Disclosure of Financial Relationships This symposium is sponsored by Chong Kun Dang Pharmaceutical Corp. I have received lecture and consultation fees from Chong Kun Dang. Pros & Cons of PPAR-γ agonist Pros Cons • Good glucose lowering • Adverse effects • Durability (ADOPT) (edema, weight gain, • Insulin sensitizing CHF, fracture or rare effects (especially in MS, macular edema etc) NAFLD, PCOS etc) • Possible safety issues • Prevention of new- (risk of MI? – Rosi or onset diabetes (DREAM, bladder cancer? - Pio) ACT-NOW) • LessSo, hypoglycemiathere is a need to develop PPAR-γ • Few GI troubles agonist• Outcome with data balanced efficacy and safety (PROactive) Insulin Sensitizers : Several Issues Rosi, Peak sale ($3.3 billion) DREAM Dr. Nissen Dr. Nissen ADOPT META analysis BARI-2D (5,8) Rosi, lipid profiles RECORD 1994 1997 1999 2000 2002 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Tro out d/t FDA, All diabetes hepatotoxicity drug CV safety Rosi (5) FDA, Black box Rosi, Rosi , CV safety warning - REMS in USA = no evidence - Europe out Pio (7) PIO, bladder cancer CKD 501 Lobeglitazone 2000.6-2004.6 2004.11-2007.1 2007.3-2008.10 2009.11-2011.04 Discovery& Preclinical study Phase I Phase II Phase III Developmental Strategy Efficacy • PPAR activity Discovery & Preclinical study • In vitro & vivo efficacy • Potent efficacy 2000.06 - 2004.06 Phase I 2004.11 - 2007.01 • In vitro screening • Repeated dose toxicity • Metabolites • Geno toxicity • Phase II CYP 450 • Reproductive toxicity 2007.03 - 2008.10 • DDI • Carcinogenic toxicity ADME Phase III Safety 2009.11 - 2011.04 CV Safety / (Bladder) Cancer / Liver Toxicity / Bone loss Lobeglitazone (Duvie) 1.
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Comparison of Clinical Outcomes and Adverse Events Associated with Glucose-Lowering Drugs in Patients with Type 2 Diabetes: a Meta-Analysis
    Online Supplementary Content Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA. doi:10.1001/jama.2016.9400. eMethods. Summary of Statistical Analysis eTable 1. Search Strategies eTable 2. Description of Included Clinical Trials Evaluating Drug Classes Given as Monotherapy eTable 3. Description of Included Clinical Trials Evaluating Drug Classes Given as Dual Therapy Added to Metformin eTable 4. Description of Included Clinical Trials Evaluating Drug Classes Given as Triple Therapy When Added to Metformin Plus Sulfonylurea eTable 5. Risks of Bias in Clinical Trials Evaluating Drug Classes Given as Monotherapy eTable 6. Risks of Bias in Clinical Trials Evaluating Drug Classes Given as Dual Therapy Added to Metformin eTable 7. Risks of Bias in Clinical Trials Evaluating Drug Classes Given as Triple Therapy When Added to Metformin plus Sulfonylurea eTable 8. Estimated Global Inconsistency in Networks of Outcomes eTable 9. Estimated Heterogeneity in Networks eTable 10. Definitions of Treatment Failure Outcome eTable 11. Contributions of Direct Evidence to the Networks of Treatments eTable 12. Network Meta-analysis Estimates of Comparative Treatment Associations for Drug Classes Given as Monotherapy eTable 13. Network Meta-analysis Estimates of Comparative Treatment Associations for Drug Classes When Used in Dual Therapy (in Addition to Metformin) eTable 14. Network Meta-analysis Estimates of Comparative Treatment Effects for Drug Classes Given as Triple Therapy eTable 15. Meta-regression Analyses for Drug Classes Given as Monotherapy (Compared With Metformin) eTable 16. Subgroup Analyses of Individual Sulfonylurea Drugs (as Monotherapy) on Hypoglycemia eTable 17.
    [Show full text]
  • Diabetes-Related Biomarkers and Methods of Use Thereof
    (19) TZZ _ _T (11) EP 2 541 254 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 21/76 (2006.01) G01N 21/64 (2006.01) 12.11.2014 Bulletin 2014/46 G01N 33/66 (2006.01) G01N 33/74 (2006.01) G01N 33/68 (2006.01) (21) Application number: 12175286.9 (22) Date of filing: 18.04.2008 (54) Diabetes-related biomarkers and methods of use thereof Diabetesassoziierte Biomarker und Verfahren zur deren Verwendung dafür Biomarqueurs associés aux diabètes et procédés d’utilisation correspondants (84) Designated Contracting States: • HANLEY ANTHONY J G ET AL: "Metabolic and AT BE BG CH CY CZ DE DK EE ES FI FR GB GR inflammation variable clusters and prediction of HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT type 2 diabetes: factor analysis using directly RO SE SI SK TR measured insulin sensitivity.", DIABETES JUL 2004, vol. 53, no. 7, July 2004 (2004-07), pages (30) Priority: 18.04.2007 US 788260 1773-1781, XP002486180, ISSN: 0012-1797 08.11.2007 US 2609 P • EDELMAN DAVID ET AL: "Utility of hemoglobin A1c in predicting diabetes risk", JOURNAL OF (43) Date of publication of application: GENERAL INTERNAL MEDICINE, vol. 19, no. 12, 02.01.2013 Bulletin 2013/01 December 2004 (2004-12), pages 1175-1180, XP002502995, ISSN: 0884-8734 (62) Document number(s) of the earlier application(s) in • INOUE ET AL: "The combination of fasting accordance with Art. 76 EPC: plasma glucose and glycosylated hemoglobin 08746276.8 / 2 147 315 predicts type 2 diabetes in Japanese workers", DIABETES RESEARCH AND CLINICAL (73) Proprietor: Health Diagnostic Laboratory, Inc.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]
  • Comparative Safety and Effectiveness of Type 2 Diabetes Medicines Final Report September 2014
    Type 2 Diabetes review – ToR 4 COMPARATIVE SAFETY AND EFFECTIVENESS OF TYPE 2 DIABETES MEDICINES FINAL REPORT SEPTEMBER 2014 A report by the Centre for Applied Health Economics (CAHE), Griffith University Type 2 Diabetes review – ToR 4 This report was commissioned by the Pharmaceutical Evaluation Branch, Department of Health, the Australian Government. Researchers: Erika Turkstra Senior research fellow, health technology assessment Martin Downes Research fellow, health technology assessment Emilie Bettington Senior research assistant Tracy Comans Senior research fellow, health technology assessment Paul Scuffham Professor and chair in health economics The assistance of Sanjeewa Kularatna with the data extraction and Gabor Mihala with the statistical analyses is appreciated. The advice provided by the Post-Market Review Section, Pharmaceutical Evaluation Branch, Department of Health and the Reference Group is also appreciated. Type 2 Diabetes review – ToR 4 CONTENTS ACRONYMS ............................................................................................................. III EXECUTIVE SUMMARY ............................................................................................ 1 PURPOSE OF THE REVIEW ........................................................................................... 1 BACKGROUND ............................................................................................................ 1 REVIEW OF CLINICAL GUIDELINES ...............................................................................
    [Show full text]
  • The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development
    International Journal of Molecular Sciences Review The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development Fan Hong 1,2, Pengfei Xu 1,*,† and Yonggong Zhai 1,2,* 1 Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China; [email protected] 2 Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China * Correspondence: [email protected] (P.X.); [email protected] (Y.Z.); Tel.: +86-156-005-60991 (P.X.); +86-10-5880-6656 (Y.Z.) † Current address: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA. Received: 22 June 2018; Accepted: 24 July 2018; Published: 27 July 2018 Abstract: Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer’s disease and ulcerative colitis. The three PPAR isoforms (α, β/δ and γ) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPARα is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia. The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks. In this review, we summarize 84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases and provide a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development.
    [Show full text]
  • Pharmaceuticals Compositions Comprising Sulphonylurea-Class Insulin Secretagogue and Polyethylene Glycol Castor Oil
    (19) & (11) EP 2 438 911 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 11.04.2012 Bulletin 2012/15 A61K 9/20 (2006.01) A61K 31/4439 (2006.01) A61K 31/64 (2006.01) A61K 9/16 (2006.01) (21) Application number: 10013440.2 (22) Date of filing: 08.10.2010 (84) Designated Contracting States: (72) Inventor: The designation of the inventor has not AL AT BE BG CH CY CZ DE DK EE ES FI FR GB yet been filed GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (74) Representative: Hodzar, Damjan et al Designated Extension States: Lek Pharmaceuticals d.d. BA ME Verovskova 57 1526 Ljubljana (SI) (71) Applicant: LEK Pharmaceuticals d.d. 1526 Ljubljana (SI) (54) Pharmaceuticals compositions comprising sulphonylurea-class insulin secretagogue and polyethylene glycol castor oil (57) The present invention relates to the field of a rea-class insulin secretagogue active pharmaceutical in- pharmaceutical technology. More specifically, the gredient and at the same time, when both formulated into present invention relates to a pharmaceutical composi- a pharmaceutical composition, ensures satisfying or ex- tion comprising sulphonylurea-class insulin secreta- ceeding other parameters like for example stability, hard- gogue and a surface active agent. Surface active agent ness, friability and handling of said pharmaceutical com- obtainable by reacting castor oil or hydrogenated castor position. oil with ethylene oxide, preferably hydrogenated castor oil, substantially improves dissolution of the sulphonylu- EP 2 438 911 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 438 911 A1 Description Field of the invention 5 [0001] The present invention relates to the field of a pharmaceutical technology.
    [Show full text]