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Imatinib Does Not Support Its Use As an Antiviral Drug
bioRxiv preprint doi: https://doi.org/10.1101/2020.11.17.386904; this version posted January 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2 Franck Touret1 *, Jean-Sélim Driouich 1, Maxime Cochin1, Paul Rémi Petit1, Magali Gilles1, Karine Barthélémy1, Grégory Moureau1, Francois-Xavier Mahon2, Denis Malvy3,4 Caroline Solas5, Xavier de Lamballerie1, Antoine Nougairède1 1 Unité des Virus Émergents (UVE: Aix-Marseille University -IRD 190-Inserm 1207-IHU Méditerranée Infection), Marseille, France. 2 Cancer Center of Bordeaux, Institut Bergonié, INSERM U1218, University of Bordeaux, Bordeaux, France. 3 Department for Infectious and Tropical Diseases, University Hospital Center of Bordeaux, Bordeaux, France. 4 Inserm 1219, University of Bordeaux, Bordeaux, France. 5 APHM, Unité des Virus Émergents (UVE: Aix Marseille University IRD 190-Inserm 1207-IHU Méditerranée Infection), Laboratoire de Pharmacocinétique et Toxicologie, Hôpital La Timone, Marseille, France. *Correspondence: Franck Touret ([email protected]) Keywords: SARS-CoV-2; Covid-19; coronavirus; antivirals; tyrosine kinase inhibitor; Imatinib bioRxiv preprint doi: https://doi.org/10.1101/2020.11.17.386904; this version posted January 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
Selective DNA-Pkcs Inhibition Extends the Therapeutic Index of Localized Radiotherapy and Chemotherapy
Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy Catherine E. Willoughby, … , Anderson J. Ryan, Stephen R. Wedge J Clin Invest. 2019. https://doi.org/10.1172/JCI127483. Research Article Oncology Therapeutics Graphical abstract Find the latest version: https://jci.me/127483/pdf The Journal of Clinical Investigation RESEARCH ARTICLE Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy Catherine E. Willoughby,1 Yanyan Jiang,2 Huw D. Thomas,1 Elaine Willmore,1 Suzanne Kyle,1 Anita Wittner,1 Nicole Phillips,1 Yan Zhao,1 Susan J. Tudhope,1 Lisa Prendergast,1 Gesa Junge,1 Luiza Madia Lourenco,2 M. Raymond V. Finlay,3 Paul Turner,3 Joanne M. Munck,4 Roger J. Griffin,5 Tommy Rennison,5 James Pickles,5 Celine Cano,5 David R. Newell,1 Helen L. Reeves,1,6 Anderson J. Ryan,2 and Stephen R. Wedge1 1Cancer Research UK Newcastle Drug Discovery Unit, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 2Cancer Research UK and UK Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom. 3Medicinal Chemistry, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom. 4Astex Pharmaceuticals, Cambridge, United Kingdom. 5Cancer Research UK Newcastle Drug Discovery Unit, Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 6Hepatopancreatobiliary Multidisciplinary Team, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Potentiating radiotherapy and chemotherapy by inhibiting DNA damage repair is proposed as a therapeutic strategy to improve outcomes for patients with solid tumors. -
Tyrosine Kinase Inhibitors and Modifications of Thyroid Function Tests
European Journal of Endocrinology (2009) 160 331–336 ISSN 0804-4643 REVIEW Tyrosine kinase inhibitors and modifications of thyroid function tests: a review Fre´de´ric Illouz1,2, Sandrine Laboureau-Soares1,Se´verine Dubois1, Vincent Rohmer1,2,3,4 and Patrice Rodien1,2,3,4 1CHU d’Angers, De´partement d’Endocrinologie Diabe´tologie Nutrition, Angers Cedex 09 F-49933, France, 2Centre de Re´fe´rence des Pathologies de la Re´ceptivite´ Hormonale, CHU d’Angers, Angers Cedex 09 F-49933, France, 3INSERM, U694, Angers Cedex 09 F-49933, France and 4Universite´ d’Angers, Angers Cedex 09 F-49933, France (Correspondence should be addressed to F Illouz; Email: [email protected]) Abstract Tyrosine kinase inhibitors (TKI) belong to new molecular multi-targeted therapies that are approved for the treatment of haematological and solid tumours. They interact with a large variety of protein tyrosine kinases involved in oncogenesis. In 2005, the first case of hypothyroidism was described and since then, some data have been published and have confirmed that TKI can affect the thyroid function tests (TFT). This review analyses the present clinical and fundamental findings about the effects of TKI on the thyroid function. Various hypotheses have been proposed to explain the effect of TKI on the thyroid function but those are mainly based on clinical observations. Moreover, it appears that TKI could alter the thyroid hormone regulation by mechanisms that are specific to each molecule. The present propositions for the management of TKI-induced hypothyroidism suggest that we assess the TFT of the patients regularly before and during the treatment by TKI. -
List Item Withdrawal Assessment Report for Folcepri
20 March 2014 EMA/CHMP/219148/2014 Committee for Medicinal Products for Human Use (CHMP) Assessment report Folcepri International non-proprietary name: etarfolatide Procedure No.: EMEA/H/C/002570/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. This AR reflects the CHMP opinion on 20 March 2014, which originally recommended to approve this medicine. The recommendation was conditional to the results of the on-going confirmatory study EC-FV-06. Before the marketing authorisation was granted by the EC, the results of this study became available and did not support the initial recommendation. Subsequently, the company decided to withdraw the application and not to pursue any longer the authorisation for marketing this product. The current report does not include the latest results of this study as the withdrawal of the application did not allow for the CHMP to revise its opinion in light of the new data. For further information please refer to the Q&A which followed the company’s withdrawal of the application. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5505 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 6 1.1. Submission of the dossier ...................................................................................... 6 1.2. Manufacturers ...................................................................................................... 8 1.3. Steps taken for the assessment of the product ......................................................... 8 2. Scientific discussion ............................................................................... -
ESMO 2014 Scientific Meeting Report
ESMO 2014 Congress Scientific Meeting Report – Lung Cancer Extract 26-30 September 2014 Madrid, Spain Summary The European Society for Medical Oncology (ESMO) Congress, held September 26 to 30 in Madrid, Spain, was a record-breaker on nearly all levels. It was resounding success and in a dedicated infographic you can find the congress statistics. A primary emphasis in the scientific programme was placed on precision medicine and how it will change the future treatment landscape in oncology. In addition, a number of scientific presentations were dedicated to cancer immunology and immunotherapy across multiple tumour types. This report is an overview of key scientific presentations made during the congress by leading international investigators. It attempts to represent the diversity and depth of the ESMO 2014 scientific programme, as well as advances in oncology. Infographic (right): ESMO 2014 record breaking Congress ESMO 2014 Congress Meeting Report Page 1 © Copyright 2014 European Society for Medical Oncology. All rights reserved worldwide. Contents Lung Cancer .................................................................................................................................... 3 Final results of the SAKK 16/00 trial: A randomised phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 NSCLC ................................................. 3 Adjuvant treatment with MAGE-A3 cancer immunotherapeutic in patients with resected NSCLC does not increase DFS: Results of the MAGRIT, a double-blind, -
Anti-Neoplastic Effects of Topoisomerase Inhibitors in Canine Mammary Carcinoma, Melanoma, and Osteosarcoma Cell Title Lines
Anti-neoplastic effects of topoisomerase inhibitors in canine mammary carcinoma, melanoma, and osteosarcoma cell Title lines Ong, Siew Mei; Yamamoto, Hiroki; Saeki, Kohei; Tanaka, Yuiko; Yoshitake, Ryohei; Nishimura, Ryohei; Nakagawa, Author(s) Takayuki Citation Japanese Journal of Veterinary Research, 65(1), 17-28 Issue Date 2017-02 DOI 10.14943/jjvr.65.1.17 Doc URL http://hdl.handle.net/2115/64788 Type bulletin (article) File Information 65-1_017-028.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Japanese Journal of Veterinary Research 65(1): 17-28, 2017 REGULAR PAPER Experimental Research Anti-neoplastic effects of topoisomerase inhibitors in canine mammary carcinoma, melanoma, and osteosarcoma cell lines Siew Mei Ong1,†), Hiroki Yamamoto1,†), Kohei Saeki1), Yuiko Tanaka1), Ryohei Yoshitake1), Ryohei Nishimura1) and Takayuki Nakagawa1,*) 1) Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan Received for publication, November 29, 2016; accepted, December 27, 2016 Abstract Numerous topoisomerase inhibitors with proven efficacy have been used extensively to treat various human neoplasms. However, among these, only doxorubicin has been used and studied extensively in veterinary oncology. The current study was performed to evaluate the responsiveness of canine osteosarcoma (cOSA), mammary gland tumour (cMGT), and malignant melanoma (cMM) cell lines to several topoisomerase inhibitors. In addition, the correlation between the sensitivity to treatment and multi-drug resistant (MDR) factors was investigated. cOSA cell lines exhibited higher sensitivity than cMGT and cMM cell lines to all the topoisomerase inhibitors tested in vitro; this was associated with the levels of multi-drug resistance protein 1 (MDR1) gene expression in the cOSA cell lines. -
CLINICAL and PHARMACOLOGICAL STUDIES on the TOPOISOMERASE I INHIBITOR TOPOTECAN Cover Design: G.L.M
CLINICAL AND PHARMACOLOGICAL STUDIES ON THE TOPOISOMERASE I INHIBITOR TOPOTECAN Cover design: G.L.M. Obbens Lay-out: A.A.C. Treuren-den Braber Printed by: Copynomie Erasmus Multicopy Facility Management B.V. Burg. Oudlaan 50 3062 PA Rotterdam The Netherlands phone: 010-4082898 fax: 010-4528183 ISBN: 9090091718 Copyright: G.J. Creemers. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanically, by photocopying, by recording or otherwise without the prior permission of the author. Clinical and pharmacological studies on the topoisomerase I inhibitor topotecan Klinisch en farmacologisch onderzoek met de topoisomerase I rammer topotecan. PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof. dr. P.W.C. Akkermans M.A. en volgens besluit van het college voor promoties. De open bare verdediging zal plaatsvinden op woensdag 13 maart 1996 om 13.45 uur door Gerardus Johannes Marie Creemers geboren te Eindhoven PROMOTIECOMMISSIE Promotor: Prof. dr. G. Stoter Copromotor: Dr. J. Verweij Overige leden: Prof. dr. D.O. Von Hoff Prof. dr. J.H. Beijnen Prof. dr. J.W. Oosterhuis Prof. dr. A. Hagenbeek "Aileen wat niet ophoudt pijn te doen, blijft in de herinnering" Contents Chapter 1 Introduction to the thesis. 1 Chapter 2 Review: The topoisomerase I inhibitors topotecan and irinotecan. 5 Cancer Treatment Reviews 1994: 20; 73·96. Chapter 3 Topotecan in colorectal cancer: A phase II study of the EORTe clinical trials group. 47 Annals of oncology 1995: 6; 844·846. -
Targeting Fibrosis in the Duchenne Muscular Dystrophy Mice Model: an Uphill Battle
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.20.427485; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Title: Targeting fibrosis in the Duchenne Muscular Dystrophy mice model: an uphill battle 2 Marine Theret1#, Marcela Low1#, Lucas Rempel1, Fang Fang Li1, Lin Wei Tung1, Osvaldo 3 Contreras3,4, Chih-Kai Chang1, Andrew Wu1, Hesham Soliman1,2, Fabio M.V. Rossi1 4 1School of Biomedical Engineering and the Biomedical Research Centre, Department of Medical 5 Genetics, 2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada 6 2Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Minia 7 University, Minia, Egypt 8 3Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, 9 Darlinghurst, NSW, 2010, Australia 10 4Departamento de Biología Celular y Molecular and Center for Aging and Regeneration (CARE- 11 ChileUC), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 12 Santiago, Chile 13 # Denotes Co-first authorship 14 15 Keywords: drug screening, fibro/adipogenic progenitors, fibrosis, repair, skeletal muscle. 16 Correspondence to: 17 Marine Theret 18 School of Biomedical Engineering and the Biomedical Research Centre 19 University of British Columbia 20 2222 Health Sciences Mall, Vancouver, British Columbia 21 Tel: +1(604) 822 0441 fax: +1(604) 822 7815 22 Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.20.427485; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
2018 Annual Report on Eudravigilance for the European Parliament, the Council and the Commission Reporting Period: 1 January to 31 December 2018
21 March 2019 EMA/906394/2019 Inspections, Human Medicines Pharmacovigilance and Committees Division 2018 Annual Report on EudraVigilance for the European Parliament, the Council and the Commission Reporting period: 1 January to 31 December 2018 Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. Table of contents Abbreviations used in the document ...................................................................................... 3 1. Executive summary ............................................................................................................ 4 2. Operation of EudraVigilance including its new functionalities ............................................ 6 3. Data collection and data quality ......................................................................................... 7 Medicinal product information ..................................................................................................... 7 Reporting of ADR reports and patient involvement ........................................................................ 7 Data Quality ............................................................................................................................. 8 4. Data analysis .................................................................................................................... -
Identification of Candidate Repurposable Drugs to Combat COVID-19 Using a Signature-Based Approach
www.nature.com/scientificreports OPEN Identifcation of candidate repurposable drugs to combat COVID‑19 using a signature‑based approach Sinead M. O’Donovan1,10, Ali Imami1,10, Hunter Eby1, Nicholas D. Henkel1, Justin Fortune Creeden1, Sophie Asah1, Xiaolu Zhang1, Xiaojun Wu1, Rawan Alnafsah1, R. Travis Taylor2, James Reigle3,4, Alexander Thorman6, Behrouz Shamsaei4, Jarek Meller4,5,6,7,8 & Robert E. McCullumsmith1,9* The COVID‑19 pandemic caused by the novel SARS‑CoV‑2 is more contagious than other coronaviruses and has higher rates of mortality than infuenza. Identifcation of efective therapeutics is a crucial tool to treat those infected with SARS‑CoV‑2 and limit the spread of this novel disease globally. We deployed a bioinformatics workfow to identify candidate drugs for the treatment of COVID‑19. Using an “omics” repository, the Library of Integrated Network‑Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID‑19 drugs and publicly available SARS‑CoV‑2 infected cell lines to identify novel therapeutics. We identifed a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID‑19, the remaining 12 have antiviral properties and 6 have antiviral efcacy against coronaviruses specifcally, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug fndings are discordant with (i.e., reverse) SARS‑CoV‑2 transcriptome signatures generated in vitro, and a subset are also identifed in transcriptome signatures generated from COVID‑19 patient samples, like the MEK inhibitor selumetinib. Overall, our fndings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID‑19 and identify promising novel targets that are worthy of further investigation. -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor -
545 © American Association of Pharmaceutical Scientists 2019 P. V
Index A Although, 524 Aberrant expression, 118 Alzheimer’s disease, 305, 326 Abluminal, 47 American type culture collection (ATCC), 537 Actin, 7 AMH, see Anti-Mullerian hormone (AMH) Actinic keratosis, 342 Aminolevulinic acid, 501 Actinomycetes, 485 Amino-triphenyl dicarboxylate-bridged Zr4+ Activated macrophages, 13 metal-organic framework nanoparticles Activation, 93 (NMOFs), 215 Activation functions (AFs), 89 Amphiregulin (AREG), 240 Active targeting, 467 β-Amyloid fibrils, 305 Adamantane–hyaluronic acid, 420 Anaplastic large cell lymphoma (ALCL), 219 Adamantane polyethylene glycol, 473 Anaplastic lymphoma kinase (ALK), 233 Adaptive immune responses, 328 Ancillary targets, 165 Adaptor proteins, 15 Androgen receptor (AR), 115 Adenocarcinoma, 231 Androgen receptor antagonists, 123 Adenomatous polyposis coli (APC), 188, 191 Androgen response elements (ARE), 116 Adenosine triphosphate (ATP), 243 Androgens, 120 Adherens junction, 179 Ang2 inhibitor (recombinant peptide-Fc- Adsorptive endocytosis, 49 fusion protein), 215 Advanced chemorefractory endometrial Angiogenesis, 53, 490, 529 cancers, 193 Angiogenesis factors, 189 Advanced epithelial ovarian, 131 Angiogenic paracrine factors, 490 Advanced gastric adenocarcinoma, 220 Anilinoquinazoline tyrosine kinase inhibitor, 242 Advanced glycation end products (AGE), 305 Annexin V, 493 Advanced/metastatic NSCLC, 258 Annexin V-FITC/propidium iodide assay, Adverse effects, 400 534–536 A glycoprotein hormone, 121 Antagonists, 287, 393 Agonists, 87 Antiangiogenic activity, 527 AIDS, 280 Antiangiogenic