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R&D UNICANCER Annual Report 2016
Going further, innovating together R&D UNICANCER Annual Report 2016 Summary Presentation and organisation Regulatory affairs, pharmaco- PAGE 01 vigilance, quality assurance – Ensuring quality and safety 2016 clinical activity in clinical trials. PAGE 08 PAGE 25 Expert groups Epidemiological Strategy and PAGE 16 Medical Economics (ESME) 2016 publications Programme – Harnessing PAGE 21 real-life data in oncology to improve patient care. Clinical operations PAGE 27 PAGE 23 Development Biological Resource and partnerships – Centre (BRC) Optimising collaborations PAGE 24 to foster innovation PAGE 30 Research in the FCCC PAGE 32 Appendices PAGE 33 Contacts, Follow us PAGE 45 GOING FURTHER, INNOVATING TOGETHER R&D ANNUAL REPORT 2016 Presentation and organisation UNICANCER, a major French player in oncology, Acteur majeur de la cancérologie française, groups together 20 French Comprehensive Cancer UNICANCER regroupe les 20 Centres de lutte contre Centers (FCCC). They are private, non-profit health la cancérologie (CLCC), établissements de santé establishments exclusively dedicated to care, research privés à but non lucratif exclusivement dédiés aux and education in cancer. UNICANCER’s R&D soins, à la recherche et à l’enseignement en cancéro- department is the driving force of UNICANCER’s logie. R&D UNICANCER en tant que promoteur research and, as an academic sponsor, it works direc- aca démi que, travaille en direct avec les unités de tly with the research units of the FCCC and other recherche des CLCC et d’autres établissements health establishments (university hospitals, hospitals de santé (CHU, CH, cliniques) en France et à l’inter- and clinics) in France and abroad. The mission of R&D national. -
WO 2018/009638 Al 11 January 2018 (11.01.2018) W !P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/009638 Al 11 January 2018 (11.01.2018) W !P O PCT (51) International Patent Classification: Published: C07D 413/14 (2006.01) A61K 31/553 (2006.01) — with international search report (Art. 21(3)) C07D 403/14 (2006.01) A61P 35/00 (2006.01) — before the expiration of the time limit for amending the (21) International Application Number: claims and to be republished in the event of receipt of PCT/US20 17/040866 amendments (Rule 48.2(h)) (22) International Filing Date: 06 July 2017 (06.07.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/359,001 06 July 2016 (06.07.2016) 62/454,163 03 February 2017 (03.02.2017) (71) Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN [US/US]; Office Of Technology Tran s fer, 1600 Huron Parkway, 2nd Floor, Ann Arbor, MI 48109-2590 (US). (72) Inventors: ROSS, Brian, D.; 2410 Foxway, Ann Arbor, MI 48105 (US). VAN DORT, Marcian; 643 Dornoch Dr., Ann Arbor, MI 48103 (US). (74) Agent: NAPOLI, James, J.; Marshall, Gerstein & Borun LLP, 233 S. Wacker Drive, 6300 Willis Tower, Chicago, IL 60606-6357 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Appendix on Tariff Elimination Schedule for Mercosur
Trade part of the EU-Mercosur Association Agreement Without Prejudice Disclaimer: In view of the Commission's transparency policy, the Commission is publishing the texts of the Trade Part of the Agreement following the agreement in principle announced on 28 June 2019. The texts are published for information purposes only and may undergo further modifications including as a result of the process of legal revision. However, in view of the growing public interest in the negotiations, the texts are published at this stage of the negotiations for information purposes. These texts are without prejudice to the final outcome of the agreement between the EU and Mercosur. The texts will be final upon signature. The agreement will become binding on the Parties under international law only after completion by each Party of its internal legal procedures necessary for the entry into force of the Agreement (or its provisional application). AR applied BR applied PY applied UY applied Mercosur Final NCM Description Comments tariff tariff tariff tariff Offer 01012100 Pure-bred horses 0 0 0 0 0 01012900 Lives horses, except pure-bred breeding 2 2 2 2 0 01013000 Asses, pure-bred breeding 4 4 4 4 4 01019000 Asses, except pure-bred breeding 4 4 4 4 4 01022110 Purebred breeding cattle, pregnant or lactating 0 0 0 0 0 01022190 Other pure-bred cattle, for breeding 0 0 0 0 0 01022911 Other bovine animals for breeding,pregnant or lactating 2 2 2 2 0 01022919 Other bovine animals for breeding 2 2 2 2 4 01022990 Other live catlle 2 2 2 2 0 01023110 Pure-bred breeding buffalo, pregnant or lactating 0 0 0 0 0 01023190 Other pure-bred breeding buffalo 0 0 0 0 0 01023911 Other buffalo for breeding, ex. -
Rediscovery of Fexinidazole
New Drugs against Trypanosomatid Parasites: Rediscovery of Fexinidazole INAUGURALDISSERTATION zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Marcel Kaiser aus Obermumpf, Aargau Basel, 2014 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist unter dem Vertrag „Creative Commons Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 3.0 Schweiz“ (CC BY-NC-ND 3.0 CH) lizenziert. Die vollständige Lizenz kann unter creativecommons.org/licenses/by-nc-nd/3.0/ch/ eingesehen werden. 1 Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel auf Antrag von Prof. Reto Brun, Prof. Simon Croft Basel, den 10. Dezember 2013 Prof. Dr. Jörg Schibler, Dekan 2 3 Table of Contents Acknowledgement .............................................................................................. 5 Summary ............................................................................................................ 6 Zusammenfassung .............................................................................................. 8 CHAPTER 1: General introduction ................................................................. 10 CHAPTER 2: Fexinidazole - A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness ........ 26 CHAPTER 3: Anti-trypanosomal activity of Fexinidazole – A New Oral Nitroimidazole Drug Candidate for the Treatment -
List of Union Reference Dates A
Active substance name (INN) EU DLP BfArM / BAH DLP yearly PSUR 6-month-PSUR yearly PSUR bis DLP (List of Union PSUR Submission Reference Dates and Frequency (List of Union Frequency of Reference Dates and submission of Periodic Frequency of submission of Safety Update Reports, Periodic Safety Update 30 Nov. 2012) Reports, 30 Nov. -
Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation
www.sciencemag.org/cgi/content/full/327/5963/348/DC1 Supporting Online Material for Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation Jason Rihel,* David A. Prober, Anthony Arvanites, Kelvin Lam, Steven Zimmerman, Sumin Jang, Stephen J. Haggarty, David Kokel, Lee L. Rubin, Randall T. Peterson, Alexander F. Schier* *To whom correspondence should be addressed. E-mail: [email protected] (A.F.S.); [email protected] (J.R.) Published 15 January 2010, Science 327, 348 (2010) DOI: 10.1126/science.1183090 This PDF file includes: Materials and Methods SOM Text Figs. S1 to S18 Table S1 References Supporting Online Material Table of Contents Materials and Methods, pages 2-4 Supplemental Text 1-7, pages 5-10 Text 1. Psychotropic Drug Discovery, page 5 Text 2. Dose, pages 5-6 Text 3. Therapeutic Classes of Drugs Induce Correlated Behaviors, page 6 Text 4. Polypharmacology, pages 6-7 Text 5. Pharmacological Conservation, pages 7-9 Text 6. Non-overlapping Regulation of Rest/Wake States, page 9 Text 7. High Throughput Behavioral Screening in Practice, page 10 Supplemental Figure Legends, pages 11-14 Figure S1. Expanded hierarchical clustering analysis, pages 15-18 Figure S2. Hierarchical and k-means clustering yield similar cluster architectures, page 19 Figure S3. Expanded k-means clustergram, pages 20-23 Figure S4. Behavioral fingerprints are stable across a range of doses, page 24 Figure S5. Compounds that share biological targets have highly correlated behavioral fingerprints, page 25 Figure S6. Examples of compounds that share biological targets and/or structural similarity that give similar behavioral profiles, page 26 Figure S7. -
Pharmaceutical Manufacturing Formulations Liquid Products V () L UME Sarfaraz K
HANDBOOK OF Pharmaceutical Manufacturing Formulations Liquid Products V () L UME Sarfaraz K. Niazi CRC PRESS Boca Raton London New York Washington, D.C. Table of Contents PART I Regulatory and Manufacturing Guidance 1 Chapter 1 Current Good Manufacturing Practice Considerations in Liquid Manufacturing 3 I. Introduction 3 II. Facilities 3 III. Equipment 3 IV. Raw Materials 4 V. Compounding 4 VI. Microbiological Quality 4 VII. Oral Suspensions 5 VIII. Product Specifications 5 IX. Process Validation 5 X. Stability 5 XI. Packaging 6 Chapter 2 Stability Testing of New Drug Substances and Products 7 I. Introduction 7 II. Drug Substance 7 A. General Case 8 B. Drug Substances Intended for Storage in a Refrigerator 8 C. Drag Substances Intended for Storage in a Freezer 8 D. Drug Substances Intended for Storage below -20°C 9 HI. Drag Product 10 A. General Case •' B. Drag Products Packaged in Impermeable Containers 11 C. Drag Products Packaged in Semipermeable Containers 11 D. Drag Products Intended for Storage in a Refrigerator 12 E. Drag Products Intended for Storage in a Freezer 13 F. Drag Products Intended for Storage below -20"C 13 IV Glossary 14 References 1() Chapter 3 Container Closure Systems '7 I. Introduction '7 A. Definitions '7 B. Current Good Manufacturing Practice, the Consumer Product Safety Commission, and Requirements on Containers and Closures 17 C. Additional Considerations 17 II. Qualification and Quality Control of Packaging Components 18 A. Description 21 B. Information about Suitability 21 C. Stability Data (Packaging Concerns) 22 D. Inhalation Drag Products 23 E. Injection and Ophthalmic Drag Products 23 F. -
Histamine Receptors
Tocris Scientific Review Series Tocri-lu-2945 Histamine Receptors Iwan de Esch and Rob Leurs Introduction Leiden/Amsterdam Center for Drug Research (LACDR), Division Histamine is one of the aminergic neurotransmitters and plays of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit an important role in the regulation of several (patho)physiological Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The processes. In the mammalian brain histamine is synthesised in Netherlands restricted populations of neurons that are located in the tuberomammillary nucleus of the posterior hypothalamus.1 Dr. Iwan de Esch is an assistant professor and Prof. Rob Leurs is These neurons project diffusely to most cerebral areas and have full professor and head of the Division of Medicinal Chemistry of been implicated in several brain functions (e.g. sleep/ the Leiden/Amsterdam Center of Drug Research (LACDR), VU wakefulness, hormonal secretion, cardiovascular control, University Amsterdam, The Netherlands. Since the seventies, thermoregulation, food intake, and memory formation).2 In histamine receptor research has been one of the traditional peripheral tissues, histamine is stored in mast cells, eosinophils, themes of the division. Molecular understanding of ligand- basophils, enterochromaffin cells and probably also in some receptor interaction is obtained by combining pharmacology specific neurons. Mast cell histamine plays an important role in (signal transduction, proliferation), molecular biology, receptor the pathogenesis of various allergic conditions. After mast cell modelling and the synthesis and identification of new ligands. degranulation, release of histamine leads to various well-known symptoms of allergic conditions in the skin and the airway system. In 1937, Bovet and Staub discovered compounds that antagonise the effect of histamine on these allergic reactions.3 Ever since, there has been intense research devoted towards finding novel ligands with (anti-) histaminergic activity. -
NON-HAZARDOUS CHEMICALS May Be Disposed of Via Sanitary Sewer Or Solid Waste
NON-HAZARDOUS CHEMICALS May Be Disposed Of Via Sanitary Sewer or Solid Waste (+)-A-TOCOPHEROL ACID SUCCINATE (+,-)-VERAPAMIL, HYDROCHLORIDE 1-AMINOANTHRAQUINONE 1-AMINO-1-CYCLOHEXANECARBOXYLIC ACID 1-BROMOOCTADECANE 1-CARBOXYNAPHTHALENE 1-DECENE 1-HYDROXYANTHRAQUINONE 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE HYDROCHLORIDE 1-NONENE 1-TETRADECENE 1-THIO-B-D-GLUCOSE 1-TRIDECENE 1-UNDECENE 2-ACETAMIDO-1-AZIDO-1,2-DIDEOXY-B-D-GLYCOPYRANOSE 2-ACETAMIDOACRYLIC ACID 2-AMINO-4-CHLOROBENZOTHIAZOLE 2-AMINO-2-(HYDROXY METHYL)-1,3-PROPONEDIOL 2-AMINOBENZOTHIAZOLE 2-AMINOIMIDAZOLE 2-AMINO-5-METHYLBENZENESULFONIC ACID 2-AMINOPURINE 2-ANILINOETHANOL 2-BUTENE-1,4-DIOL 2-CHLOROBENZYLALCOHOL 2-DEOXYCYTIDINE 5-MONOPHOSPHATE 2-DEOXY-D-GLUCOSE 2-DEOXY-D-RIBOSE 2'-DEOXYURIDINE 2'-DEOXYURIDINE 5'-MONOPHOSPHATE 2-HYDROETHYL ACETATE 2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID 2-METHYLFLUORENE 2-METHYL-2-THIOPSEUDOUREA SULFATE 2-MORPHOLINOETHANESULFONIC ACID 2-NAPHTHOIC ACID 2-OXYGLUTARIC ACID 2-PHENYLPROPIONIC ACID 2-PYRIDINEALDOXIME METHIODIDE 2-STEP CHEMISTRY STEP 1 PART D 2-STEP CHEMISTRY STEP 2 PART A 2-THIOLHISTIDINE 2-THIOPHENECARBOXYLIC ACID 2-THIOPHENECARBOXYLIC HYDRAZIDE 3-ACETYLINDOLE 3-AMINO-1,2,4-TRIAZINE 3-AMINO-L-TYROSINE DIHYDROCHLORIDE MONOHYDRATE 3-CARBETHOXY-2-PIPERIDONE 3-CHLOROCYCLOBUTANONE SOLUTION 3-CHLORO-2-NITROBENZOIC ACID 3-(DIETHYLAMINO)-7-[[P-(DIMETHYLAMINO)PHENYL]AZO]-5-PHENAZINIUM CHLORIDE 3-HYDROXYTROSINE 1 9/26/2005 NON-HAZARDOUS CHEMICALS May Be Disposed Of Via Sanitary Sewer or Solid Waste 3-HYDROXYTYRAMINE HYDROCHLORIDE 3-METHYL-1-PHENYL-2-PYRAZOLIN-5-ONE -
PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 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. -
Pp-03-25-New Dots.Qxd 10/23/02 2:38 PM Page 379
pp-03-25-new dots.qxd 10/23/02 2:38 PM Page 379 HYDROGEN SULFIDE 379 HYDROGEN SULFIDE [7783-06-4] Formula: H2S; MW 34.08 Synonyms: sulfur hydride; sulfureted hydrogen Occurrence and Uses Hydrogen sulfide occurs in natural gas. It also is found in many sewer gases. It is a by-product of many industrial processes. Trace amounts of dis- solved H2S are found in wastewaters in equilibrium with dissolved sulfides and hydrosulfides. It also is found in volcanic eruptions, hot springs and in troposphere. The average concentration of H2S in the air is about 0.05 ppb. The most important applications of hydrogen sulfide involve the production of sodium sulfide and other inorganic sulfides. Hydrogen sulfide obtained as a by-product often is converted into sulfuric acid. It also is used in organic syn- thesis to make thiols or mercaptans. Other applications are in metallurgy for extracting nickel, copper, and cobalt as sulfides from their minerals; and in classical qualitative analytical methods for precipitation of many metals (see Reactions). It also is used in producing heavy water for nuclear reactors. Physical Properties Colorless gas; characteristic odor of rotten eggs; odor threshold 1ppm; sweetish taste; fumes in air; flammable gas, burns with a pale blue flame; refractive index at 589.3nm, 1.000644 at 0°C and 1 atm; density 1.539 g/L at 0°C; critical temperature 100.4°C; critical pressure 88.9 atm; liquefies at –60.7°C; solidifies at –85.5°C; velocity of sound 289 m/sec in H2S gas; slightly soluble in water (0.4% at 20°C); pH of a saturated aqueous solution 4.5; slight- ly acidic; diffusivity in water at 16°C, 1.77x105 cm2/sec; soluble in carbon disulfide, methanol, acetone; very soluble in N-methylpyrrolidinone and alka- nolamines (salt formation occurs: salt dissociates on heating); liquid H2S dis- solves sulfur and SO2. -
Vitiligo Treatment
ISSN 2320-5407 International Journal of Advanced Research (2014) Journal homepage: http://www.journalijar.com INTERNATIONAL JOURNAL OF ADVANCED RESEARCH Depigmentation Therapy for Vitiligo: Results from a National Survey Dissertation submitted to Libyan International Medical University In partial fulfillment of the requirements For the award of the degree of Bachelor of Pharmacy BY Makpula Abdelaziz Tarhuni Aisha Ali Derbash Under The Guidance of Dr. Salma Bukhatwa 1 ISSN 2320-5407 International Journal of Advanced Research (2014) Declaration This is to certify that research work embodied in this thesis entitled "Depigmentation therapy of vitiligo: Results from a national survey" has been carried out by us under supervision of Dr. Salma Bukhatwa. Makpula Abdelaziz Tarhuni ................................................... Aisha Ali Derbash ...................................................... 2 ISSN 2320-5407 International Journal of Advanced Research (2014) Abstract Vitiligo is a chronicpigmentarydisorderthat causes the loss of skin color in blotches. Vitiligo happens because of destruction of melanocytes. Classification of vitiligo according to distribution of the lesions is of practical importance usually for assessing the prognosis of the disease. Repigmentation therapyfor vitiligo includes corticosteroids, topical and oral antioxidants, topical calcineurin inhibitors, phototherapy and laser therapy. Depigmentation therapy can be beneficial as alternative therapy for extensive vitiligo patients. Depigmentation therapyof vitiligo