DOCSLIB.ORG

European Pharmaceuticals Pharmaceuticals Industry Update

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Deutsche Bank Markets Research Europe Industry Date United Kingdom 29 August 2012 Pharmaceuticals European Pharmaceuticals Pharmaceuticals Industry Update Jeremy Lai, MD Tim Race, CFA Research Analyst Research Analyst (+44) 20 754-58441 (+44) 207 54-76522 [email protected] [email protected] Pharmaceuticals for Beginners 2012 Mark Clark Research Analyst (+44) 20 754-75875 [email protected] Richard Parkes, Ph.D Research Analyst (+44) 20 754-50470 [email protected] Holger Blum, DVFA Research Analyst (+41) 44 227-3376 [email protected] ________________________________________________________________________________________________________________ Deutsche Bank AG/London All prices are those current at the end of the previous trading session unless otherwise indicated. Prices are sourced from local exchanges via Reuters, Bloomberg and other vendors. Data is sourced from Deutsche Bank and subject companies. Deutsche Bank does and seeks to do business with companies covered in its research reports. Thus, investors should be aware that the firm may have a conflict of interest that could affect the objectivity of this report. Investors should consider this report as only a single factor in making their investment decision. DISCLOSURES AND ANALYST CERTIFICATIONS ARE LOCATED IN APPENDIX 1. MICA(P) 072/04/2012. Deutsche Bank Markets Research Europe Industry Date United Kingdom 29 August 2012 Pharmaceuticals European Pharmaceuticals Pharmaceuticals Industry Update Jeremy Lai, MD Tim Race, CFA Research Analyst Research Analyst Pharmaceuticals for Beginners 2012 (+44) 20 754-58441 (+44) 207 54-76522 [email protected] [email protected] Welcome to the 2012 edition of Pharmaceuticals for Beginners Mark Clark So, you’ve inherited the pharmaceutical sector. Big companies, large market Research Analyst capitalisations and interesting diseases with some funny-sounding names. (+44) 20 754-75875 Fantastic! You finally get to follow a sector that might actually be of interest to [email protected] the person sitting next to you at a dinner party. But wait. What is a GLP-1 analogue, and why can’t analysts just say heart Richard Parkes, Ph.D attack or heartburn instead of using lengthy terms like myocardial infarction or Research Analyst gastro-oesophageal reflux disorder? And what on earth is a randomised, (+44) 20 754-50470 placebo-controlled, double-blind, Phase III clinical trial anyway? Oh no, what [email protected] have I gotten myself into? Holger Blum, DVFA In our view, the pharmaceutical industry is fascinating, exciting and of obvious Research Analyst relevance beyond the stock market. But it is also very technical and comprises (+41) 44 227-3376 a minefield of products, scientific terms and disease pathways. Keeping track [email protected] of it all can at times prove bewildering, and not just for the uninitiated. With this in mind, the pharmaceuticals team at Deutsche Bank first published a document in January 2001 that was targeted at beginners and industry veterans alike – “Pharmaceuticals for Beginners”. The first and subsequent editions were such a success that we are now publishing our 2012 edition, which has been completely updated, while retaining much influence from the original. This report is structured in two parts, with the first providing an introduction to the industry dynamics and regulatory framework governing pharmaceuticals, and the second containing an introduction to the different therapeutic markets. The current edition covers 32 disease areas, including new topics such as Pulmonary Arterial Hypertension and Epilepsy. We have also included overviews on topics such as emerging markets, vaccines, orphan genetic diseases, consumer health and animal health. “Pharmaceuticals for Beginners” is not necessarily intended to be read cover to cover, but is meant as an easy-to-use reference guide. Although our intent was to provide professionals who are new to the pharmaceuticals sector with an introduction to a complex industry, we hope that our more learned readers will find new insights as well. Overall, we hope that this book will be a valuable resource that might find its own spot on many overcrowded desks. ________________________________________________________________________________________________________________ Deutsche Bank AG/London All prices are those current at the end of the previous trading session unless otherwise indicated. Prices are sourced from local exchanges via Reuters, Bloomberg and other vendors. Data is sourced from Deutsche Bank and subject companies. Deutsche Bank does and seeks to do business with companies covered in its research reports. Thus, investors should be aware that the firm may have a conflict of interest that could affect the objectivity of this report. Investors should consider this report as only a single factor in making their investment decision. DISCLOSURES AND ANALYST CERTIFICATIONS ARE LOCATED IN APPENDIX 1. MICA(P) 072/04/2012. 29 August 2012 Pharmaceuticals European Pharmaceuticals Industry Overview Introduction .................................................................................... 5 The companies ............................................................................. 14 Leading drugs ............................................................................... 24 Research ....................................................................................... 29 Research glossary ........................................................................ 36 Genomics and biotechnology ....................................................... 37 Regulation .................................................................................... 43 Funding and pricing of pharmaceuticals ...................................... 51 Generic drugs ............................................................................... 69 Patents and market exclusivity ..................................................... 74 Biosimilars .................................................................................... 80 US patent litigation ....................................................................... 84 US legislative process .................................................................. 90 Legislative dictionary .................................................................... 94 Pharmaceutical marketing............................................................ 97 Emerging markets ...................................................................... 105 Consumer healthcare ................................................................. 119 Animal health ............................................................................. 122 Vaccines ..................................................................................... 126 Companion diagnostics .............................................................. 131 Page 2 Deutsche Bank AG/London 29 August 2012 Pharmaceuticals European Pharmaceuticals Therapeutic review Introduction to cardiovascular disorders .................................... 139 Hyperlipidaemia.......................................................................... 140 Thrombosis ................................................................................. 146 Hypertension .............................................................................. 153 Pulmonary arterial hypertension ................................................ 158 Diabetes mellitus ........................................................................ 163 Erectile dysfunction .................................................................... 174 GERD and peptic ulcer disease .................................................. 177 Asthma ....................................................................................... 181 Chronic obstructive pulmonary disorder .................................... 188 Allergic rhinitis ............................................................................ 194 Osteoporosis............................................................................... 198 Pain ............................................................................................. 203 Rheumatoid arthritis ................................................................... 207 Transplantation and immunosuppression .................................. 212 Antibiotics .................................................................................. 218 Human immunodeficiency virus (HIV)........................................ 224 Viral hepatitis .............................................................................. 231 Influenza ..................................................................................... 237 Introduction to CNS disorders .................................................... 240 Schizophrenia ............................................................................. 242 Parkinson’s disease .................................................................... 248 Alzheimer’s disease .................................................................... 252 Depression and affective disorders ............................................ 256 Attention deficit hyperactivity disorder (ADHD) ......................... 260 Multiple sclerosis ........................................................................ 264 Epilepsy ...................................................................................... 270 Migraine ....................................................................................
Recommended publications
  • Endothelin System and Therapeutic Application of Endothelin Receptor

    Endothelin System and Therapeutic Application of Endothelin Receptor

    xperim ACCESS Freely available online & E en OPEN l ta a l ic P in h l a C r m f o a c l a o n l o r g u y o J Journal of ISSN: 2161-1459 Clinical & Experimental Pharmacology Research Article Endothelin System and Therapeutic Application of Endothelin Receptor Antagonists Abebe Basazn Mekuria, Zemene Demelash Kifle*, Mohammedbrhan Abdelwuhab Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia ABSTRACT Endothelin is a 21 amino acid molecule endogenous potent vasoconstrictor peptide. Endothelin is synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonic, and inflammatory cells. It acts through a seven transmembrane endothelin receptor A (ETA) and endothelin receptor B (ETB) receptors belongs to G protein-coupled rhodopsin-type receptor superfamily. This peptide involved in pathogenesis of cardiovascular disorder like (heart failure, arterial hypertension, myocardial infraction and atherosclerosis), renal failure, pulmonary arterial hypertension and it also involved in pathogenesis of cancer. Potentially endothelin receptor antagonist helps the treatment of the above disorder. Currently, there are a lot of trails both per-clinical and clinical on endothelin antagonist for various cardiovascular, pulmonary and cancer disorder. Some are approved by FAD for the treatment. These agents are including both selective and non-selective endothelin receptor antagonist (ETA/B). Currently, Bosentan, Ambrisentan, and Macitentan approved
  • THELIN, INN-Sitaxentan Sodium

    THELIN, INN-Sitaxentan Sodium

    European Medicines Agency Evaluation of Medicines for Human Use London, 17 December 2009 Doc. Ref EMA/831836/2009 ASSESSMENT REPORT FOR Thelin International non-proprietary name/Common name: sitaxentan sodium EMEA/H/C/000679/II/0018 Variation Assessment Report as adopted by theauthorised CHMP with all information of a commercially confidential nature deleted longer no product Medicinal 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 13 E-mail: [email protected] http://www.ema.europa.eu European Medicines Agency, 2009. Reproduction is authorised provided the source is acknowledged. I. SCIENTIFIC DISCUSSION 1.1. Introduction Thelin contains sitaxentan sodium, which is an endothelin receptor antagonist, with higher selectivity for the ETA receptor than the ETB receptor subtype. Endothelin-1 (ET-1) is a potent vascular paracrine and autocrine peptide in the lung, and can also promote fibrosis, cell proliferation, cardiac hypertrophy and remodeling, and is pro-inflammatory. ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension (PAH), as well as other cardiovascular disorders and connective tissue diseases, including scleroderma, acute and chronic heart failure, myocardial ischaemia, systemic hypertension, and atherosclerosis, suggesting a pathogenic role of ET- 1 in these diseases. In PAH and heart failure, in the absence of endothelin receptor antagonism, elevated ET-1 concentrations are strongly correlated with the severity and prognosis of these diseases. Additionally, PAH is also characterised by reduced nitric oxide activity. ET-1 actions are mediated through endothelin A receptors (ETA), present on smooth muscle cells, and endothelin B receptors (ETB), present on endothelial cells.
  • Corrigendum Doi:10.1093/Eurheartj/Ehr046

    Corrigendum Doi:10.1093/Eurheartj/Ehr046

    Corrigendum doi:10.1093/eurheartj/ehr046 ............................................................................................................................................................................. Corrigendum to: ‘Guidelines for the diagnosis and treatment of pulmonary hypertension’ [European Heart Journal (2009) 30, 2493–2537]. The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Authors/Task Force Members: Nazzareno Galie` (Chairperson) (Italy); Marius M. Hoeper (Germany); Marc Humbert (France); Adam Torbicki (Poland); Jean-Luc Vachiery (France); Joan Albert Barbera (Spain); Maurice Beghetti (Switzerland); Paul Corris (UK); Sean Gaine (Ireland); J. Simon Gibbs (UK); Miguel Angel Gomez-Sanchez (Spain); Guillaume Jondeau (France); Walter Klepetko (Austria) Christian Opitz (Germany); Andrew Peacock (UK); Lewis Rubin (USA); Michael Zellweger (Switzerland); Gerald Simonneau (France). Withdrawal of sitaxentan in the treatment of pulmonary arterial hypertension The 2009 ESC Practice Clinical Guidelines for the diagnosis and treatment of pulmonary hypertension included the endothelin receptor antag- onist sitaxentan in an algorithm of evidence-based treatment for pulmonary arterial hypertension. Sitaxentan was recommended with a Class I/Level A grade of evidence in WHO functional class III patients and Class IIa/Level C grade of evidence
  • 05/01/02 Louisiana Medicaid Management

    05/01/02 Louisiana Medicaid Management

    APPENDIX C 05/01/02 LOUISIANA MEDICAID MANAGEMENT INFORMATION SYSTEM PAGE 1 DEPT OF HEALTH AND HOSPITALS - BUREAU OF HEALTH SERVICES FINANCING LOUISIANA MEDICAID PHARMACY BENEFITS MANAGEMENT UNIT ONLY THESE COMPANIES PRODUCTS ARE COVERED AND ONLY THOSE DOSAGE FORMS LISTED IN APPENDIX A. MEDICAID DRUG FEDERAL REBATE PARTICIPATING PHARMACEUTICAL COMPANIES LABELER PHARMACEUTICAL COMPANY EFFECTIVE END DATE CODE DATE 00002 ELI LILLY & CO 04/01/91 00003 E.R.SQUIBB & SONS,INC 04/01/91 00004 HOFFMAN-LA ROCHE,INC 04/01/91 00005 LEDERLE LABORATORIES AMERICAN CYANAMID 04/01/91 00006 MERCK SHARP & DOHME 04/01/91 00007 SMITHKLINE BEECHAM CORPORATION 04/01/91 00008 WYETH LABORATORIES 04/01/91 00009 THE UPJOHN COMPANY 04/01/91 00011 BECTON DICKINSON MICROBIOLOGY SYSTEMS 10/01/91 07/01/98 00013 ADRIA LABORATORIES DIV.OF ERBAMONT,INC 04/01/91 00014 G.D.SEARLE & CO 04/01/91 01/01/01 00015 MEAD JOHNSON & COMPANY 04/01/91 00016 KABI PHARMACIA 04/01/91 00021 REED & CARNRICK 10/01/96 01/01/97 00023 ALLERGAN,INC 04/01/91 00024 WINTHROP PHARMACEUTICALS 04/01/91 00025 G.D.SEARLE & CO 04/01/91 00026 MILES INC.,PHARMACEUTICAL DIVISION 04/01/91 00028 GEIGY PHARMACEUTICALS 04/01/91 00029 SMITHKLINE BEECHAM CORPORATION 04/01/91 00031 ROBINS,A.H. 04/01/91 00032 SOLVAY PHARMACEUTICALS 04/01/91 00033 SYNTEX 04/01/91 00034 THE PURDUE FREDERICK COMPANY 04/01/91 00037 CARTER-WALLACE,INC 04/01/91 00038 STUART PHARMACEUTICALS,ICI AMERICAS INC 04/01/91 07/01/01 00039 HOECHST-ROUSSEL PHARMACEUTICALS INC 04/01/91 00043 SANDOZ CONSUMER CORPORATION 04/01/91 00044 KNOLL PHARMACEUTICALS
  • Overview of Ftc Antitrust Actions in Pharmaceutical Services and Products

    Overview of Ftc Antitrust Actions in Pharmaceutical Services and Products

    OVERVIEW OF FTC ANTITRUST ACTIONS IN PHARMACEUTICAL SERVICES AND PRODUCTS Health Care Division Bureau of Competition Federal Trade Commission Washington D.C. 20580 Markus H. Meier Assistant Director Bradley S. Albert Deputy Assistant Director Saralisa C. Brau Deputy Assistant Director September 2009 TABLE OF CONTENTS Page I. INTRODUCTION. ........................................................... 1 II. CONDUCT INVOLVING PHARMACEUTICAL SERVICES AND PRODUCTS. 3 A. Monopolization. ...................................................... 3 B. Agreements Not to Compete. ............................................ 8 C. Agreements on Price or Price-Related Terms. 14 D. Agreements to Obstruct Innovative Forms of Health Care Delivery or Financing. 20 E. Illegal Tying and Other Arrangements. .................................... 20 III. PHARMACEUTICAL MERGERS. ........................................... 20 A. Horizontal Mergers Between Direct Competitors. 20 B. Potential Competition Mergers. ......................................... 44 C. Innovation Market Mergers. ............................................ 47 D. Vertical Mergers...................................................... 49 IV. INDUSTRY GUIDANCE STATEMENTS...................................... 50 A. Advisory Opinions. ................................................... 50 B. Citizen Petition to the Food and Drug Administration. 51 V. AMICUS BRIEFS. ......................................................... 51 VI. INDICES. ............................................................
  • WHO Drug Information Vol

    WHO Drug Information Vol

    WHO Drug Information Vol. 24, No. 4, 2010 World Health Organization WHO Drug Information Contents WHO Prequalification Sitaxentan: worldwide withdrawal 307 Programmes Sibutramine: suspension of sales 307 Sibutramine-containing medicines: WHO Prequalification of Medicines withdrawal 308 Programme: survey of service Testosterone transdermal patch: quality provided to manufacturers 293 withdrawal of extension of WHO initiates pilot prequalification of indication application 308 active pharmaceutical ingredients 297 Aliskiren/valsartan: withdrawal of New on-line database for WHO marketing authorization application 308 prequalified vaccines 298 Mometasone furoate/formoterol fumarate: withdrawal of marketing Safety and Efficacy Issues authorization application 309 EMA and US FDA extend confidentiality H1N1 influenza vaccine: narcolepsy 299 arrangements indefinitely 309 Statins: interstitial lung disease 299 Tocilizumab: risk of fatal anaphylaxis 300 Recent Publications, Pioglitazone: potential bladder cancer 301 Information and Events Angiotensin receptor blockers and US Government to share patents with cancer: safety review 301 Medicines Patent Pool 310 GnRH agonists, diabetes and cardio- Clinical trials and global medicines vascular disease 301 development 310 Gadolinium-based contrast agents: Evaluation of future nanomedicines 311 kidney dysfunction 302 Reporting on opioid inaccessibility 311 Lamotrigine: aseptic meningitis Tinzaparin sodium: renal Impairment in elderly 303 Consultation Documents Tamoxifen: drug interactions involving The
  • Access to New Medicines in New Zealand Compared to Australia

    Access to New Medicines in New Zealand Compared to Australia

    THE NEW ZEALAND MEDICAL JOURNAL Journal of the New Zealand Medical Association Access to new medicines in New Zealand compared to Australia Michael Wonder, Richard Milne Abstract Aim To compare access to new prescription-only medicines in New Zealand (NZ) with that in Australia. Method The range of new prescription medicines and the timing of their regulatory approval and reimbursement in NZ and Australia in the period 2000 to 2009 were compared. Results 136 new prescription medicines were first listed in the Australian Schedule of Pharmaceutical Benefits in the study period and 59 (43%) of these were listed in the NZ Pharmaceutical Schedule. Listing of these 59 medicines for reimbursement occurred later in NZ (mean difference=32.7 months; 95% CI 24.2 to 41.2 months; p<0.0001) due largely to a longer time from registration to listing (mean difference=23.7 months; 95% CI 14.9 to 32.4 months; p<0.0001). The remaining 77 medicines that are reimbursed in Australia but not in NZ cover a wide range of therapeutic areas, including some diseases for which there are no reimbursed medicines in NZ. Four new medicines were listed in NZ but not Australia. Conclusion In the last decade, public access to new medicines in NZ has been more limited and delayed compared to Australia. Access to new medicines is an ongoing public health issue in most developed countries. Many new medicines are costly and unaffordable for many patients; therefore public access is very limited. Governments are under continual pressure to provide timely access to new medicines, many of which are costly.
  • Modifications to the Harmonized Tariff Schedule of the United States To

    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).
  • 2018 Medicines in Development for Skin Diseases

    2018 Medicines in Development for Skin Diseases

    2018 Medicines in Development for Skin Diseases Acne Drug Name Sponsor Indication Development Phase ADPS topical Taro Pharmaceuticals USA acne vulgaris Phase II completed Hawthorne, NY www.taro.com AOB101 AOBiome acne vulgaris Phase II (topical ammonia oxidizing bacteria) Cambridge, MA www.aobiome.com ASC-J9 AndroScience acne vulgaris Phase II (androgen receptor degradation Solana Beach, CA www.androscience.com enhancer) BLI1100 Braintree Laboratories acne vulgaris Phase II completed Braintree, MA www.braintreelabs.com BPX-01 BioPharmX acne vulgaris Phase II (minocycline topical) Menlo Park, CA www.biopharmx.com BTX1503 Botanix Pharmaceuticals moderate to severe acne vulgaris Phase II (cannabidiol) Plymouth Meeting, PA www.botanixpharma.com CJM112 Novartis Pharmaceuticals acne vulgaris Phase II (IL-17A protein inhibitor) East Hanover, NJ www.novartis.com clascoterone Cassiopea acne vulgaris Phase III (androgen receptor antagonist) Lainate, Italy www.cassiopea.com Medicines in Development: Skin Diseases ǀ 2018 Update 1 Acne Drug Name Sponsor Indication Development Phase CLS001 Cutanea acne vulgaris Phase II (omiganan) Wayne, PA www.cutanea.com DFD-03 Promius Pharma acne vulgaris Phase III (tazarotene topical) Princeton, NJ www.promiuspharma.com DMT310 Dermata Therapeutics moderate to severe acne vulgaris Phase II (freshwater sponge-derived) San Diego, CA www.dermatarx.com finasteride Elorac severe nodulocystic acne Phase II (cholestenone 5-alpha Vernon Hills, IL www.eloracpharma.com reductase inhibitor) FMX101 Foamix moderate to severe
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1

    Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1

    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
  • Crth2: Can Residence Time Help ?

    Crth2: Can Residence Time Help ?

    CRTh2: Can Residence Time Help ? RSC-SCI Cambridge Medicinal Chemistry Symposium Churchill College, Cambridge 8-11 September 2013 Rick Roberts Almirall Introduction Paul Ehrlich, The Lancet (1913), 182, 445 “A substance will not work unless it is bound” 100 years on: “What a substance does may depend on how long it is bound” 2 In a nutshell …. Introduction “Applications of Binding Kinetics to Drug Discovery” D. Swinney, Pharm. Med. (2008), 22, 23-34 3 Energetic concept of Residence Time kon Standard model [R] + [L] [RL] k unbound off bound Energy ‡ Binding process (kon) is (R·L) determined by the energy barrier Ea E Ligand concentration a Unbinding process (koff) is determines the number of Ed determined by the energy attempts to get over this barrier Ed barrier [R] + [L] G = Ed -Ea [RL] Reaction coordinate Potency (Ki) is determined by the difference in these energies koff Ki = kon 4 K , k , k i on off -1 -1 kon M s Potency (nM) vs kon vs koff Very fast association 108 10 1 0.1 0.01 0.001 107 100 10 1 0.1 0.01 0.001 fast association 106 1000 100 10 1 0.1 0.01 0.001 105 10 M 1000 100 10 1 0.1 0.01 0.001 slow association 104 10 M 1000 100 10 1 0.1 0.01 Very slow association 103 10 M 1000 100 10 1 0.1 “inactive” 102 10 M 1000 100 10 1 10 10-1 10-2 10-3 10-4 10-5 10-6 10-7 s-1 koff Energy A simple binding measurement gives no clue to how fast the association and dissociation are (R·L)‡ Very slow associating compounds that are very slow dissociating (R·L)‡ slow associating compounds that are slow dissociating Are all fast associating compounds
  • Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic Kidney Disease: a Rose with Many Thorns Michael N

    Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic Kidney Disease: a Rose with Many Thorns Michael N

    Himmelfarb Health Sciences Library, The George Washington University Health Sciences Research Commons Medicine Faculty Publications Medicine 2013 Endothelin receptor antagonists (ERA) in hypertension and chronic kidney disease: A rose with many thorns Michael N. Doumas George Washington University V. Athyros Aristotle University of Thessaloniki N. Katsiki Aristotle University of Thessaloniki A. Reklou Aristotle University of Thessaloniki A. Lazaridis Aristotle University of Thessaloniki See next page for additional authors Follow this and additional works at: http://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs Part of the Medicine and Health Sciences Commons Recommended Citation Doumas, M., Athyros, V., Katsiki, N., Reklou,A., Lazaridis, A., Karagiannis, A. (2013). Endothelin receptor antagonists (ERA) in hypertension and chronic kidney disease: A rose with many thorns. Open Hypertension Journal, 5, 12-17. This Journal Article is brought to you for free and open access by the Medicine at Health Sciences Research Commons. It has been accepted for inclusion in Medicine Faculty Publications by an authorized administrator of Health Sciences Research Commons. For more information, please contact [email protected]. Authors Michael N. Doumas, V. Athyros, N. Katsiki, A. Reklou, A. Lazaridis, and A. Karagiannis This journal article is available at Health Sciences Research Commons: http://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/ 322 Send Orders for Reprints to [email protected] 12 The Open Hypertension Journal, 2013, 5, 12-17 Open Access Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic Kidney Disease: a Rose with Many Thorns Doumas M1,2,*, Athyros V1, Katsiki N1, Reklou A1, Lazaridis A1 and Karagiannis A1 12nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece 2VAMC and George Washington University, Washington, DC, USA Abstract: The discovery of endothelin created a lot of enthusiasm and paved new therapeutic avenues for the treatment of arterial hypertension.