DOCSLIB.ORG

NDO Home | Contact | Register for NDO Access

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

NNeewwsslleetttteerr Highlights of updates to NDO in February 2014 NDO home | Contact | Register for NDO access in Prescribing Regulatory changes in the EU Outlook 2013 Launched in the UK Botulinum toxin A (Botox) Stroke-associated ankle disability [licence extension] Canagliflozin (Invokana) Type 2 diabetes mellitus in adults Cobicistat (Tybost) HIV infection in adults Dimethyl fumarate (Tecfidera) Multiple sclerosis, relapsing-remitting Dolutegravir (Tivicay) HIV infection in adults and adolescents from age 12 years Elvitegravir (Vitekta) HIV infection in adults Lipegfilgrastim (Lonquex) Chemotherapy-induced neutropenia Sofosbuvir (Sovaldi) Hepatitis C infection in adults Solifenacin + tamsulosin (Vesomni) Benign prostatic hyperplasia-associated lower urinary tract symptoms [new formulation] Ulipristal (Esmya) Uterine fibroids – repeat three-month treatment course after previous pre-operative treatment of moderate to severe symptoms [licence extension] Approved in the EU Autologous cultured chondrocytes Full-thickness cartilage defects of the knee in adults (MACI) Brimonidine (Mirvaso) Rosacea facial erythema in adults [new formulation] Ethinylestradiol + gestodene Contraception [transdermal formulation] Somatropin Growth hormone deficiency [once-weekly formulation] EU positive opinions Budesonide + formoterol (DuoResp Asthma and chronic obstructive pulmonary disease [new formulation] Spiromax) Canagliflozin + metformin IR Type 2 diabetes mellitus (Vokanamet) Elosulfase alfa (Vimizim) Mucopolysaccharidosis IVA (Morquio syndrome) Follicle stimulating hormone In vitro fertilisation biosimilar (Bemfola) Propranolol (Hemangiol) Proliferating infantile haemangioma [new formulation] Rituximab (MabThera) Non-Hodgkin's lymphoma [subcutaneous formulation] Umeclidinium (Incruse) Chronic obstructive pulmonary disease Umeclidinium + vilanterol (Anoro) Chronic obstructive pulmonary disease Filed for approval in the EU Apixaban (Eliquis) Treatment of deep vein thrombosis and pulmonary embolism, and prevention of their recurrence [licence extension] Cangrelor Prevention of thrombosis in patients undergoing CABG Ciclosporin (Restasis) Keratoconjunctivitis sicca, moderate-to-severe [new formulation] To access New Drugs Online monographs click on the drug name/indication or visit www.ukmi.nhs.uk/ndo Direct links to abbreviated NDO monographs via NICE Evidence Search are included Complete monographs are password protected and can be viewed at www.ukmi.nhs.uk/ndo In February 2014 | 576 monographs updated | 34 evidence-based evaluations added | 3,797 registered NDO users Newsletter Newsletter Filed for approval in the EU (continued) Dinutuximab (Unituxin) Neuroblastoma in children Indacaterol + glycopyrronium bromide Asthma [licence extension] (Ultibro Breezhaler) Levofloxacin (Aeroquin) Cystic fibrosis-associated Pseudomonas aeruginosa infection [new formulation] Liraglutide (Victoza) Type 2 diabetes mellitus – in combination with basal insulin [licence extension] Lisdexamfetamine dimesylate (Elvanse) Attention-deficit hyperactivity disorder, newly-diagnosed in adults [licence extension] Netupitant + palonosetron Chemotherapy-induced nausea and vomiting [new formulation] Oritavancin (Nuvocid) Complicated bacterial skin and skin structure infections Sofosbuvir + ledipasvir Chronic hepatitis C virus genotype 1 infection in adults [new formulation] Tedizolid phosphate Acute bacterial skin and skin structure infections Other EU developments Amikacin liposomal (Arikace) Nontuberculous mycobacterial lung disease – issued a positive opinion for orphan drug status Ataluren (Translarna) Duchenne muscular dystrophy – company requests re-examination of negative opinion Eculizumab (Soliris) Prevention of delayed graft function after solid organ transplantation – granted orphan drug status Hepatitis B vaccine (Heplisav) Hepatitis B – filing withdrawn Icatibant (Firazyr) ACE inhibitor-induced angioedema – filing withdrawn Masitinib (Masiviera) Pancreatic cancer, advanced – company requests re-examination of negative opinion Ridaforolimus (Jenzyl) Breast cancer / Endometrial cancer / Prostate cancer / Soft tissue and bone sarcoma – development discontinued Sofosbuvir + ledipasvir Chronic hepatitis C virus genotype 1 infection in adults – opinion on a compassionate use programme announced Tanezumab Osteoarthritis – development suspended New monographs added (27) Phase in EU Afuresertib Multiple myeloma – combination therapy None (PII US) Bevacizumab biosimilar – ABP 215 Non-small cell lung cancer, advanced PIII c1 inhibitor (human) (Cinryze) Hereditary angioedema – prophylaxis in children aged 6 to 11 PIII Delafloxacin Uncomplicated urogenital gonorrhoea None (PIII US) EBI-005 Dry eye None (PIII US) EMA401 Postherpetic neuralgia None Evolocumab Homozygous familial hypercholesterolaemia PIII Febuxostat (Adenuric) Tumour lysis syndrome PII Gantenerumab Alzheimer’s disease, mild PIII Ibodutant Irritable bowel syndrome, diarrhoea-predominant PII Insulin glargine biosimilar – MK-1293 Type 1 and type 2 diabetes mellitus PIII IPI-145 Chronic lymphocytic leukaemia or small cell lymphoma, refractory PIII or relapsed If you do not wish to continue receiving NDO Newsletter log in and update your profile at www.ukmi.nhs.uk/ndo In February 2014 | 576 monographs updated | 34 evidence-based evaluations added | 3,797 registered NDO users This is an NHS document not to be used for commercial purposes Newsletter Newsletter New monographs added (continued) Phase in EU ISIS-SMNRx Spinal muscular atrophy PII Losmapimod Acute coronary syndrome PII Lubiprostone (Amitiza) Irritable bowel syndrome, constipation-predominant, in women None (Launched US) Masitinib Prostate cancer, metastatic, castrate-resistant – first-line PIII combination therapy Mepolizumab Eosinophilic granulomatosis with polyangiitis PIII Mercaptamine bitartrate Huntington's disease PIII Muscle derived cells-urethral sphincter Stress incontinence PIII repair Nivolumab Non-small cell lung cancer, stage IV or recurrent PD-L1 – first-line PIII OMS824 Huntington’s disease PII Palbociclib Breast cancer in patients at high risk of recurrence post- PIII neoadjuvant therapy PBT2 Huntington's disease None (PII US) Ragweed allergy therapy (Ragwitek) Allergic rhinitis None (Positive opinion US) Ramucirumab (Cyramza) Colorectal cancer – second-line combination therapy PIII Ramucirumab (Cyramza) Non-small cell lung cancer – second-line combination therapy PIII Recombinant human antithrombin iii Pre-eclampsia None (PIII US) (ATryn) Focus: Drugs in development for lung cancer Phase in EU Non-small cell lung cancer Afatinib (Giotrif) Oral dual EGFR and HER2 inhibitor – second-line in squamous disease PIII / / third or fourth-line Suspended Alectinib Oral ALK inhibitor PII Apricoxib (Capoxigem) Oral selective COX-2 inhibitor PII Astuprotimut-R IM oncology vaccine PIII Bavituximab IV angiogenesis inhibitor PIII Belagenpumatucel-L (Lucanix) Intradermal antisense-DNA vaccine PIII Belinostat Oral HDAC inhibitor PII Bevacizumab (Avastin) IV VEGF antagonist – adjuvant therapy PIII Bevacizumab biosimilar – ABP 215 IV VEGF antagonist PIII Ceritinib Oral ALK inhibitor – first-line / second plus-line PIII / PIII Cisplatin liposomal (Nanoplatin) IV formulation that delivers cisplatin directly into cancer cells PIII Custirsen IV clusterin inhibitor and antisense oligonucleotide PIII Dabrafenib (Tafinlar) Oral BRAF inhibitor PII Dacomitinib Oral pan-HER inhibitor – first-line / second-line PIII / PIII Dimesna (Tavocept) IV antioxidant PIII Entinostat Oral histone deacetylase inhibitor PII If you do not wish to continue receiving NDO Newsletter log in and update your profile at www.ukmi.nhs.uk/ndo In February 2014 | 576 monographs updated | 34 evidence-based evaluations added | 3,797 registered NDO users This is an NHS document not to be used for commercial purposes Newsletter Newsletter Focus: Drugs in development for lung cancer Phase in EU Non-small cell lung cancer (continued) Erlotinib (Tarceva) Oral EGFR inhibitor – adjuvant therapy / maintenance treatment PIII / Filed Fosbretabulin (Zybrestat) IV cadherin 5 inhibitor PII Ganetespib IV heat shock protein 90 inhibitor PIII Gefitinib (Iressa) Oral EGFR inhibitor – second-line after first-line gefitinib PIII Ipilimumab (Yervoy) IV human antibody against CTLA-4 PIII Lambrolizumab IV humanised monoclonal IgG4 antibody against PD-1 protein PIII MPDL3280A IV immunotherapy involving PD-L1 protein PIII Necitumumab IV EGFR antagonist – non-squamous / squamous PIII / PIII Nimotuzumab (Theraloc) IV EGFR-targeting monoclonal antibody None (PII US) Nintedanib (Vargatef) Oral VEGFR-2, fibroblast growth factor receptor and platelet-derived Filed growth factor receptor inhibitor Nivolumab IV PDCD 1 inhibitor – first-line / second-line PIII / PIII Onartuzumab IV monovalent 5D5 anti-c-Met monoclonal antibody PIII Paclitaxel albumin-bound (Abraxane) IV tubulin inhibitor – first-line / maintenance PIII / None (PIII US) Pralatrexate (Folotyn) IV apoptosis stimulant, dihydrofolate reductase inhibitor and DNA PII synthesis inhibitor Ramucirumab (Cyramza) IV VEGFR-2 antagonist PIII Selumetinib Oral selective and uncompetitive MEK kinase inhibitor PIII Talactoferrin alfa Oral dendritic cell recruiter and activator PIII Tecemotide (Stimuvax) SC cancer vaccine – induces a specific immune response to MUC-1 PIII Tergenpumatucel-L (HyperAcute Lung) Intradermal immunotherapy None (PIII US) Tertomotide Intradermal telomerase vaccine None (PIII US) TG4010 SC therapeutic vaccine PIII Vinflunine (Javlor) IV vinca-alkaloid microtubule inhibitor PIII Small cell lung cancer Amrubicin (Calsed) IV topoisomerase II inhibitor Unknown Ipilimumab (Yervoy) IV human antibody against CTLA-4 PIII Palifosfamide (Zymafos) IV alkylating agent PII Reovirus (Reolysin) IV immunomodulator None (PII US) If you do not wish to continue receiving NDO Newsletter log in and update your profile at www.ukmi.nhs.uk/ndo In February 2014 | 576 monographs updated | 34 evidence-based evaluations added | 3,797 registered NDO users This is an NHS document not to be used for commercial purposes .
Recommended publications
  • WO 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT

    WO 2018/223101 Al 06 December 2018 (06.12.2018) 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 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT (51) International Patent Classification: (71) Applicant: JUNO THERAPEUTICS, INC. [US/US]; 400 A 61K 35/1 7 (20 15.0 1) A 61P 35/00 (2006 .0 1) Dexter Ave. N., Suite 1200, Seattle, WA 98109 (US). (21) International Application Number: (72) Inventor: ALBERTSON, Tina; 400 Dexter Ave. N., Suite PCT/US2018/035755 1200, Seattle, WA 98109 (US). (22) International Filing Date: (74) Agent: AHN, Sejin et al; Morrison & Foerster LLP, 1253 1 0 1 June 2018 (01 .06.2018) High Bluff Drive, Suite 100, San Diego, CA 92130-2040 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of national protection available): AE, AG, AL, AM, (30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/5 14,774 02 June 2017 (02.06.2017) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/5 15,530 05 June 2017 (05.06.2017) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/521,366 16 June 2017 (16.06.2017) u s HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/527,000 29 June 2017 (29.06.2017) u s KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 62/549,938 24 August 2017 (24.08.2017) u s MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/580,425 0 1 November 2017 (01 .11.2017) u s OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/593,871 0 1 December 2017 (01 .12.2017) u s SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/596,764 08 December 2017 (08.12.2017) u s TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
  • Emerging Pharmacological Strategies for the Treatment

    Emerging Pharmacological Strategies for the Treatment

    Emerging pharmacological strategies for the treatment of fibromyalgia LAWSON, Kim Available from Sheffield Hallam University Research Archive (SHURA) at: http://shura.shu.ac.uk/15300/ This document is the author deposited version. You are advised to consult the publisher's version if you wish to cite from it. Published version LAWSON, Kim (2017). Emerging pharmacological strategies for the treatment of fibromyalgia. World Journal of Pharmacology, 6 (1), 1-10. Repository use policy Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in SHURA to facilitate their private study or for non- commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain. Sheffield Hallam University Research Archive http://shura.shu.ac.uk World Journal of WJ P Pharmacology Submit a Manuscript: http://www.wjgnet.com/esps/ World J Pharmacol 207 March 9; 6(): -0 DOI: 0.5497/wjp.v6.i. ISSN 2220-392 (online) MINIREVIEWS Emerging pharmacological strategies for the treatment of ibromyalgia Kim Lawson Kim Lawson, Department of Biosciences and Chemistry, Bio­ presenting with a complex of symptoms dominated by molecular Sciences Research Centre, Shefield Hallam University, chronic widespread pain associated with the existence of a Faculty of Health and Wellbeing, Sheffield S1 1WB, United range of co-morbidities, such as fatigue, sleep disturbance, Kingdom cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and nor- Author contributions: Lawson K researched the materials for the article and wrote the manuscript.
  • Physiologically Based Pharmacokinetic Modeling in Regulatory Decision‐Making at the European Medicines Agency

    Physiologically Based Pharmacokinetic Modeling in Regulatory Decision‐Making at the European Medicines Agency

    ARTICLES Physiologically Based Pharmacokinetic Modeling in Regulatory Decision-Making at the European Medicines Agency E Luzon1, K Blake1, S Cole2,3,4, A Nordmark4,5, C Versantvoort3,6 and E Gil Berglund3,5 Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision- making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE WHAT THIS STUDY ADDS TO OUR KNOWLEDGE TOPIC? þ This is the first work presenting the situation in the Europe- þ PBPK is a cutting-edge technology that is increasingly being an Union and confirms what was detected by the FDA is a applied to drug development to address various aspects related global trend. to clinical pharmacology. Previous works by the FDA acknowl- HOW THIS MIGHT CHANGE CLINICAL PHARMA- edge its use in regulatory submissions in the US, but so far there COLOGY OR TRANSLATIONAL SCIENCE is no analysis of the European perspective.
  • Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr

    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr

    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
  • Related Kinases (VRK) Bound to Small-Molecule Inhibitors Identifies Different P-Loop Conformations

    Related Kinases (VRK) Bound to Small-Molecule Inhibitors Identifies Different P-Loop Conformations

    Structural characterization of human Vaccinia- Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations Rafael M. Couñago1,2*, Charles K. Allerston3, Pavel Savitsky3, Hatylas Azevedo4, Paulo H Godoi1,5, Carrow I. Wells6, Alessandra Mascarello4, Fernando H. de Souza Gama4, Katlin B. Massirer1,2, William J. Zuercher6, Cristiano R.W. Guimarães4 and Opher Gileadi1,3 1. Structural Genomics Consortium, Universidade Estadual de Campinas — UNICAMP, Campinas, SP, Brazil. 2. Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, Campinas, SP, Brazil. 3. Structural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, UK. 4. Aché Laboratórios Farmacêuticos SA, Guarulhos, SP, Brazil. 5. Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, Brazil. 6. Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA. *Correspondence to Rafael M. Couñago: [email protected] (RMC) Supplementary information 1 SUPPLEMENTARY METHODS PKIS results analyses - hierarchical cluster analysis (HCL) A hierarchical clustering (HCL) analysis was performed to group kinases based on their inhibition patterns across the compounds. The average distance clustering method was employed, using sample tree selection and sample leaf order optimization. The distance metric used was the Pearson correlation and the HCL analysis was performed in the TmeV software 1. SUPPLEMENTARY REFERENCES 1 Saeed, A. I. et al. TM4: a free, open-source system for microarray data management and analysis. BioTechniques 34, 374-378, (2003). SUPPLEMENTARY FIGURES LEGENDS Supplementary Figure S1: Hierarchical clustering analysis of PKIS data. Hierarchical clustering analysis of PKIS data.
  • Sarcoma Metabolomics: Current Horizons and Future Perspectives

    Sarcoma Metabolomics: Current Horizons and Future Perspectives

    cells Review Sarcoma Metabolomics: Current Horizons and Future Perspectives Miguel Esperança-Martins 1,2,3,* , Isabel Fernandes 1,3,4 , Joaquim Soares do Brito 4,5, Daniela Macedo 6, Hugo Vasques 4,7, Teresa Serafim 2, Luís Costa 1,3,4 and Sérgio Dias 2,4 1 Centro Hospitalar Universitário Lisboa Norte, Medical Oncology Department, Hospital Santa Maria, 1649-028 Lisboa, Portugal; [email protected] (I.F.); [email protected] (L.C.) 2 Vascular Biology & Cancer Microenvironment Lab, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; tserafi[email protected] (T.S.); [email protected] (S.D.) 3 Translational Oncobiology Lab, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal 4 Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; [email protected] (J.S.d.B.); [email protected] (H.V.) 5 Centro Hospitalar Universitário Lisboa Norte, Orthopedics and Traumatology Department, Hospital Santa Maria, 1649-028 Lisboa, Portugal 6 Medical Oncology Department, Hospital Lusíadas Lisboa, 1500-458 Lisboa, Portugal; [email protected] 7 General Surgery Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisboa, Portugal * Correspondence: [email protected] Abstract: The vast array of metabolic adaptations that cancer cells are capable of assuming, not Citation: Esperança-Martins, M.; only support their biosynthetic activity, but also fulfill their bioenergetic demands and keep their Fernandes, I.; Soares do Brito, J.; intracellular reduction–oxidation (redox) balance. Spotlight has recently been placed on the en- Macedo, D.; Vasques, H.; Serafim, T.; ergy metabolism reprogramming strategies employed by cancer cells to proliferate.
  • G Protein-Coupled Receptors

    G Protein-Coupled Receptors

    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading.
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set

    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
  • GPCR/G Protein

    GPCR/G Protein

    Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com GPCR/G Protein G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In unstimulated cells, the state of G alpha is defined by its interaction with GDP, G beta-gamma, and a GPCR. Upon receptor stimulation by a ligand, G alpha dissociates from the receptor and G beta-gamma, and GTP is exchanged for the bound GDP, which leads to G alpha activation. G alpha then goes on to activate other molecules in the cell. These effects include activating the MAPK and PI3K pathways, as well as inhibition of the Na+/H+ exchanger in the plasma membrane, and the lowering of intracellular Ca2+ levels. Most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system. A series of studies showed that aberrant GPCR Signaling including those for GPCR-PCa, PSGR2, CaSR, GPR30, and GPR39 are associated with tumorigenesis or metastasis, thus interfering with these receptors and their downstream targets might provide an opportunity for the development of new strategies for cancer diagnosis, prevention and treatment. At present, modulators of GPCRs form a key area for the pharmaceutical industry, representing approximately 27% of all FDA-approved drugs. References: [1] Moreira IS. Biochim Biophys Acta. 2014 Jan;1840(1):16-33.
  • Withdrawal Assessment Report for Jenzyl, INN: RIDAFOROLIMUS

    Withdrawal Assessment Report for Jenzyl, INN: RIDAFOROLIMUS

    3 December 2012 EMA/774827/2012 Committee for Medicinal Products for Human Use (CHMP) Withdrawal Assessment report for Jenzyl International non-proprietary name: Ridaforolimus Procedure no EMEA/H/C/2259 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. This withdrawal Assessment Report is based on the latest assessment report adopted by the CHMP with all information of a commercially confidential nature deleted. This should be read in conjunction with the “Questions and Answers” document on the withdrawal of the application: the Assessment Report may not include all available information on the product if the CHMP assessment of the latest submitted information was still ongoing at the time of the withdrawal of the application. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8613 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged. 1. RECOMMENDATION Based on the CHMP review of the data and the Applicant’s response to the CHMP LOQ on quality, safety and efficacy, the CHMP considers that the application for Jenzyl, an orphan medicinal product, in the treatment metastatic soft tissue sarcoma or bone sarcoma as maintenance therapy for patients who have completed at least 4 cycles of chemotherapy without evidence of disease progression in adult and paediatric patients aged 13 through 17 years with weight over 100 pounds or 45.4 kilograms). is not approvable since "major objections" still remain, which preclude a recommendation for marketing authorisation at the present time.
  • Phenotype-Based Drug Screening Reveals Association Between Venetoclax Response and Differentiation Stage in Acute Myeloid Leukemia

    Phenotype-Based Drug Screening Reveals Association Between Venetoclax Response and Differentiation Stage in Acute Myeloid Leukemia

    Acute Myeloid Leukemia SUPPLEMENTARY APPENDIX Phenotype-based drug screening reveals association between venetoclax response and differentiation stage in acute myeloid leukemia Heikki Kuusanmäki, 1,2 Aino-Maija Leppä, 1 Petri Pölönen, 3 Mika Kontro, 2 Olli Dufva, 2 Debashish Deb, 1 Bhagwan Yadav, 2 Oscar Brück, 2 Ashwini Kumar, 1 Hele Everaus, 4 Bjørn T. Gjertsen, 5 Merja Heinäniemi, 3 Kimmo Porkka, 2 Satu Mustjoki 2,6 and Caroline A. Heckman 1 1Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki; 2Hematology Research Unit, Helsinki University Hospital Comprehensive Cancer Center, Helsinki; 3Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; 4Department of Hematology and Oncology, University of Tartu, Tartu, Estonia; 5Centre for Cancer Biomarkers, De - partment of Clinical Science, University of Bergen, Bergen, Norway and 6Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, Helsinki, Finland ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2018.214882 Received: December 17, 2018. Accepted: July 8, 2019. Pre-published: July 11, 2019. Correspondence: CAROLINE A. HECKMAN - [email protected] HEIKKI KUUSANMÄKI - [email protected] Supplemental Material Phenotype-based drug screening reveals an association between venetoclax response and differentiation stage in acute myeloid leukemia Authors: Heikki Kuusanmäki1, 2, Aino-Maija
  • WHO Drug Information Vol

    WHO Drug Information Vol

    WHO Drug Information Vol. 26, No. 4, 2012 WHO Drug Information Contents International Regulatory Regulatory Action and News Harmonization New task force for antibacterial International Conference of Drug drug development 383 Regulatory Authorities 339 NIBSC: new MHRA centre 383 Quality of medicines in a globalized New Pakistan drug regulatory world: focus on active pharma- authority 384 ceutical ingredients. Pre-ICDRA EU clinical trial regulation: public meeting 352 consultation 384 Pegloticase approved for chronic tophaceous gout 385 WHO Programme on Tofacitinib: approved for rheumatoid International Drug Monitoring arthritis 385 Global challenges in medicines Rivaroxaban: extended indication safety 362 approved for blood clotting 385 Omacetaxine mepesuccinate: Safety and Efficacy Issues approved for chronic myelo- Dalfampridine: risk of seizure 371 genous leukaemia 386 Sildenafil: not for pulmonary hyper- Perampanel: approved for partial tension in children 371 onset seizures 386 Interaction: proton pump inhibitors Regorafenib: approved for colorectal and methotrexate 371 cancer 386 Fingolimod: cardiovascular Teriflunomide: approved for multiple monitoring 372 sclerosis 387 Pramipexole: risk of heart failure 372 Ocriplasmin: approved for vitreo- Lyme disease test kits: limitations 373 macular adhesion 387 Anti-androgens: hepatotoxicity 374 Florbetapir 18F: approved for Agomelatine: hepatotoxicity and neuritic plaque density imaging 387 liver failure 375 Insulin degludec: approved for Hypotonic saline in children: fatal diabetes mellitus