DOCSLIB.ORG

W O 2016/028826 A1 25 February 2016 (25.02.2016) W IPO I PCT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
W O 2016/028826 A1 25 February 2016 (25.02.2016) W IPO I 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 W O 2016/028826 A1 25 February 2016 (25.02.2016) W IPO I PCT (51) International Patent Classification: (74) Agents: SWISS, Gerald F. et al.; Foley & Lardner, LLP, A61K38/22 (2006.01) 3579 Valley Centre Drive, Suite 300, San Diego, Califor (21) International Application Number: nia 92130 (US). PCT/US2015/045777 (81) Designated States (unless otherwise indicated,for every ) .a kind of national protection available): AE, AG, AL, AM, (22) International Filng Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 18 August 2015 (18.08.2015) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (25) Filing Language: English DO, DZ, EC, EE, EG, ES, Fl, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (26) Publication Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (30) Priority Data: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 62/039,358 19 August 2014 (19.08.2014) US PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 62/046,748 5 September 2014 (05.09.2014) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/050,690 15 September 2014 (15.09.2014) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 62/057,181 29 September 2014 (29.09.2014) US (84) Designated States (unless otherwise indicated,for every 62/057,184 29 September 2014 (29.09.2014) US kind of regional protection available): ARIPO (BW, GH, 62/063,897 14 October 2014 (14.10.2014) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/108,948 28 January 2015 (28.01.2015) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, 62/118,423 19 February 2015 (19.02.2015) US TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 62/192,448 14 July 2015 (14.07.2015) US DK, EE, ES, Fl, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, 62/201,530 5 August 2015 (05.08.2015) US LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (71) Applicant: OXEIA BIOPHARMACEUTICALS, INC. SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, [US/US]; 12463 Carmel Park Drive, San Diego, California GW, KM, ML, MR, NE, SN, TD, TG). 92130 (US). Published: (72) Inventors: SHAH, Kartik Kiran; c/o Oxeia Biopharma- with internationalsearch report (Art. 21(3)) ceuticals, Inc., 12463 Carmel Park Drive, San Diego, Cali fornia 92130 (US). MUNSHI, Amit Dilip; c/o Oxeia Bio- before the expiration of the time limit for amending the pharmaceuticals, Inc., 12463 Carmel Park Drive, San claims and to be republished in the event of receipt of Diego, California 92130 (US). amendments (Rule 48.2(h)) (54) Title: METHODS OF TREATING MILD BRAIN INJURY (57) Abstract: The present disclosure provides methods for treating mild brain injury and other neurological disorders in a subject in f4 need thereof, comprising administering to the subject an effective amount of a compound comprising a ghrelin or ghrelin variant. This invention provides for methods for treating a mild brain injury or concussion in a patient wherein said method comprises ad ministering to the subject in need thereof suffering from said mild brain injury or concussion an effective amount of a ghrelin variant or a composition comprising a ghrelin variant so as to treat said mild brain injury or concussion. WO 2016/028826 PCT/US2015/045777 METHODS OF TREATING MILD BRAIN INJURY CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims benefit of priority to U.S. Provisional Application No. 62/039,358, filed August 19, 2014, U.S. Provisional Application No. 62/046,748, filed September 05, 2014, U.S. Provisional Application No. 62/050,690, filed September 15, 2014, U.S. Provisional Application No. 62/057,181, filed September 29, 2014, U.S. Provisional Application No. 62/057,184, filed September 29, 2014, U.S. Provisional Application No. 62/063,897, filed October 14, 2014, U.S. Provisional Application No. 62/108,948, filed January 28, 2015, U.S. Provisional Application No. 62/118,423, filed February 19, 2015, U.S. Provisional Application No. 62/192,448, filed July 14, 2015, U.S. Provisional Application No. 62/201,530, filed August 5, 2015, the disclosures of each of which are incorporated herein by reference in their entireties. FIELD OF THE INVENTION [0002] The present disclosure provides methods for treating mild brain injuries, concussion, and other neurological disorders arising from such an injury in a subject in need thereof by administering to the subject an effective amount of a composition comprising a ghrelin variant. BACKGROUND [0003] Mild brain injuries (mBI), typically including concussions, having "your bell rung", and the like, describe an insult to the brain that, in turn, can cause long term injury to the brain. It most often occurs from direct contact to the head, but can also result from indirect injury (e.g., whiplash injury or violent shaking of the head). Individuals who have suffered one brain injury are more at risk for a second brain injury and more susceptible for subsequent injuries. The damage from successive mBIs is cumulative (Cantu, R. C, Second-impact syndrome, Clinics in Sports Medicine, 17(l):37-44, 1998). [0004] The long term damage arising from mBI include cognitive and motor skill deterioration such as psychomotor slowing, poor concentration and attention retrieval resulting in increased 1 WO 2016/028826 PCT/US2015/045777 variability of performance, and overall executive dysfunction (Stuss et al., Adult Clinical Neuropsychology: Lessons from Studies of the Frontal Lobes, Annual Review of Psychology, 53, 401-433 (2003)). Common examples of the long term effect of mBI are found in soldiers, boxers, football players, soccer players, and the like. Well documented examples are individuals who, long after the occurrence of the mBl(s), begin to manifest the cumulative damage to the brain by loss of one or more cognitive skills and/or motor skills. [0005] The difference between mBI and other brain diseases is that mBI is caused by one or more injuries as opposed to a disease. In the former case, the injuries to the brain cannot be attributed to an underlying pathology but, rather, are the results of the injuries. [0006] Ghrelin is a neuroendocrine hormone that acts as an endogenous ligand for growth hormone secretagogue receptor. It is a 28-amino acid and an endogenously produced peptide predominantly secreted by gastric mucosa. It has been referred to as the "hunger hormone," due to its well-studied effects on appetite, but it also is believed to play a significant role in regulating the distribution and rate of use of energy. [0007] Regardless, the majority of brain injuries is considered mild in nature and arise from non-disease related phenomena. To date, there has been little to no credible treatment of such mild brain injuries (mBI). Thus, there is a significant unmet need for a therapy for treating mBI that does not impose undesirable costs and delays and are effective. As provided below, this invention is predicated upon the discovery of a profound and surprising effect of ghrelin variants and analogs in the treatment of mBl. Such treatments can be easily administered without delays for individuals suffering from mBI to ensure that they are capable of performing certain tasks safely without risk to themselves or others. SUMMARY OF THE INVENTION [0008] This invention provides for methods for treating a mild brain injury or concussion in a patient wherein said method comprises administering to the subject in need thereof suffering from said mild brain injury or concussion an effective amount of a ghrelin variant or a 2 WO 2016/028826 PCT/US2015/045777 composition comprising a ghrelin variant so as to treat said mild brain injury or concussion. In one embodiment, the ghrelin variant is administered in a non-endogenous carrier. [0009] In some embodiments, the ghrelin variants can be a sequence that includes any of a number of modifications to the wild type ghrelin sequence, which comprises a polypeptide having an amino acid sequence of Gly-Ser-Ser-Phe-Leu-Ser-Pro-Glu-His-Gln-Arg-Val-Gln-Gln Arg-Lys-Glu-Ser-Lys-Lys-Pro-Pro-Ala-Lys-Leu-Gln-Pro-Arg (SEQ ID NO. 1). Non-limiting examples of potential modifications include modifying the length (shorter or longer) of the sequences, modifying the chemistry of the amino acids, substituting one or more of the amino acids with another amino acid, a synthetic amino acid or otherwise rare or non-naturally occurring amino acid, introducing protecting groups at the N and/or C termini, etc. In some embodiments, the polypeptide is modified with one or more fatty acids. In some embodiments, the fatty acid is an octanoic acid. In some embodiments, the polypeptide is modified at serine at amino acid position 2 and/or serine at amino acid position 3 of SEQ ID No. 1. [0010] For example, in some embodiments, the ghrelin variants include C-C 20 acylation of the carboxyl group of one or both of the glutamic acid residues or of the C-terminus arginine group. In other embodiments, ghrelin variants include C-C2 0 acylation of one or more of the hydroxyl groups of the serine residues. Yet, in other embodiments, ghrelin variants include replacing one or more of the L-amino acids with a D-amino acid.
Load more

Recommended publications
  • United States Patent 1191 Lll] 3,983,266 Bahls [451 Sept
    United States Patent 1191 lll] 3,983,266 Bahls [451 Sept. 28, 1976 [54] METHOD FOR APPLYING METALLIC 3.776.740 [2/1973 Sivcrz ct al. .......................... .. l06/l SILVER TO A SUBSTRATE OTHER PUBLICATIONS [75] Inventor: Harry Bahls, Wayne, Pa. lvanov et al., Chem. Abs. 43:2548c, I949, [73] Assignee: Peacock Laboratories, Inc., Philadelphia, Pa. Primary Examiner-Ralph S. Kendall [22] Filed: Oct. 9, I974 I 57] ABSTRACT [2!] ,Appl. No.: 513,417 High efficiency deposition of silver on the surface of a substrate is obtained by providing a solution contain [52] [1.8. CI ............................... .. 427/164; 427/165; ing reducible dissolved silver in the presence of an al 427/168; 427/424; 427/426; l06/l kali metal hydroxide and ammonia, all of which are [51] Int. CLZ. ......................................... .. C23C 3/02 applied to the substrate in the presence of an aqueous [58] Field of Search .............. .. l06/l; 427/l68. I69, solution of a moderating reducer containing :1 poly 427/165, I64, 426, 304, 125, 425 hydric alcohol of the formula CH2OH(CHOH),,C H,OH, where n is an integer from 1 to 6. Preferably [56] References Cited the polyhydric alcohol is sorbitol, and in a preferred UNITED STATES PATENTS embodiment a moderator is the form of a thio glycerol is present. 2,996,406 8/l96l Weinrich ........... ............ .. 427/168 3,772,078 ll/l973 Polichcttc ct al ................. .. l06/l X l5 Claims, No Drawings 3,983,266 1 Other objects and advantages of this invention, in METHOD FOR APPLYING METALLIC SILVER TO cluding the economy of the same, and the case with A SUBSTRATE which it may be applied to existing silver coating equip ment and apparatus, will further become apparent BRIEF SUMMARY OF THE INVENTION 5 hereinafter.
    [Show full text]
  • Pharmacological Agents Currently in Clinical Trials for Disorders in Neurogastroenterology
    Pharmacological agents currently in clinical trials for disorders in neurogastroenterology Michael Camilleri J Clin Invest. 2013;123(10):4111-4120. https://doi.org/10.1172/JCI70837. Clinical Review Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in understanding the mechanisms of these disorders, through basic and translational research, and in targeting the receptors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients’ symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastroparesis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain. Find the latest version: https://jci.me/70837/pdf Review Pharmacological agents currently in clinical trials for disorders in neurogastroenterology Michael Camilleri Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA. Esophageal, gastrointestinal, and colonic diseases resulting from disorders of the motor and sensory functions represent almost half the patients presenting to gastroenterologists. There have been significant advances in under- standing the mechanisms of these disorders, through basic and translational research, and in targeting the recep- tors or mediators involved, through clinical trials involving biomarkers and patient responses. These advances have led to relief of patients’ symptoms and improved quality of life, although there are still significant unmet needs. This article reviews the pipeline of medications in development for esophageal sensorimotor disorders, gastropa- resis, chronic diarrhea, chronic constipation (including opioid-induced constipation), and visceral pain.
    [Show full text]
  • Biochemistry Lab (BT35L) Lab Manual
    Department of Biotechnology Sri Jayachamarajendra College of Engineering Mysuru-570006 Biochemistry Lab (BT35L) Lab Manual (Prepared by Dr. S. Nanjunda Swamy and Dr. M. N. Nagendra Prasad) INDEX 1. PREPARATION OF SODIUM ACETATE BUFFER 2. ESTIMATION OF GLUCOSE BY DNS METHOD 3. ESTIMATION OF SAPONIFICATION VALUE OF FATS/OILS 4. ESTIMATION OF ACID VALUE OF FATS/OILS 5. PREPARATION OF PHOSPHOTIDYL CHOLINE FROM EGG YOLK 6. LOWRY METHOD FOR PROTEIN ESTIMATION 7. ESTIMATION OF AMINO ACID BY FORMAL TITRATION 8. DETERMINATION OF ISOELECTRIC POINT OF GLYCINE (PI) 9. SEPARATION OF AMINO ACIDS BY CIRCLULAR PAPER CHROMATOGRAPHY 10. ESTIMATION OF IRON BY WONG’S METHOD Experiment No 1: PREPARATION OF SODIUM ACETATE BUFFER Aim: Preparation of sodium acetate buffer of 0.1M and 4.7 pH (25ml) Principle: Buffer is a solution used to maintain the pH of any biochemical reaction. Procedure: 1. Weigh about 0.205g of sodium acetate. Dissolve it in 15ml distilled water. 2. Dip the electrode of the pre calibrated pH meter in the above solution. 3. Add acetic acid of 0.5M drop by drop till the pH reaches 4.7. 4. Make up the solution to 25ml with distilled water. 5. Store the buffer in a sealed container. Experiment No 2: ESTIMATION OF GLUCOSE BY DNS METHOD Aim: To estimate the amount of glucose in the given ample by DNS method. Principle: This method tests for the presence of free carbonyl group (C=O), of the reducing sugars. The reaction involves the oxidation of this of free carbonyl group (aldehyde functional group present in, glucose and the ketone functional group in fructose) and simultaneous reduction of , 3,5-dinitrosalicylic acid to 3-amino,5- nitrosalicylic acid (a coloured molecule) under alkaline conditions.
    [Show full text]
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [Show full text]
  • 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
    [Show full text]
  • ( 12 ) United States Patent
    US010317418B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 ,317 ,418 B2 Goosens (45 ) Date of Patent: * Jun . 11 , 2019 (54 ) USE OF GHRELIN OR FUNCTIONAL 7 , 479 ,271 B2 1 / 2009 Marquis et al . GHRELIN RECEPTOR AGONISTS TO 7 ,632 , 809 B2 12 / 2009 Chen 7 ,666 , 833 B2 2 /2010 Ghigo et al. PREVENT AND TREAT STRESS -SENSITIVE 7 , 901 ,679 B2 3 / 2011 Marquis et al . PSYCHIATRIC ILLNESS 8 ,013 , 015 B2 9 / 2011 Harran et al . 8 ,293 , 709 B2 10 /2012 Ross et al . (71 ) Applicant: Massachusetts Institute of 9 ,724 , 396 B2 * 8 / 2017 Goosens A61K 38 /27 9 , 821 ,042 B2 * 11 /2017 Goosens .. A61K 39/ 0005 Technology , Cambridge , MA (US ) 10 , 039 ,813 B2 8 / 2018 Goosens 2002/ 0187938 A1 12 / 2002 Deghenghi (72 ) Inventor : Ki Ann Goosens, Cambridge , MA (US ) 2003 / 0032636 Al 2 /2003 Cremers et al. 2004 / 0033948 Al 2 / 2004 Chen ( 73 ) Assignee : Massachusetts Institute of 2005 / 0070712 A1 3 /2005 Kosogof et al. Technology , Cambridge , MA (US ) 2005 / 0148515 Al 7/ 2005 Dong 2005 / 0187237 A1 8 / 2005 Distefano et al. 2005 /0191317 A1 9 / 2005 Bachmann et al. ( * ) Notice : Subject to any disclaimer , the term of this 2005 /0201938 A1 9 /2005 Bryant et al. patent is extended or adjusted under 35 2005 /0257279 AL 11 / 2005 Qian et al. U . S . C . 154 ( b ) by 0 days. 2006 / 0025344 Al 2 /2006 Lange et al. 2006 / 0025566 A 2 /2006 Hoveyda et al. This patent is subject to a terminal dis 2006 / 0293370 AL 12 / 2006 Saunders et al .
    [Show full text]
  • Anorexia Nervosa and Endocrinology: a Clinical Update Støving, René Klinkby
    University of Southern Denmark MECHANISMS IN ENDOCRINOLOGY Anorexia nervosa and endocrinology: a clinical update Støving, René Klinkby Published in: European Journal of Endocrinology DOI: 10.1530/EJE-18-0596 Publication date: 2019 Document version: Final published version Document license: CC BY Citation for pulished version (APA): Støving, R. K. (2019). MECHANISMS IN ENDOCRINOLOGY: Anorexia nervosa and endocrinology: a clinical update. European Journal of Endocrinology, 180(1), R9-R27. https://doi.org/10.1530/EJE-18-0596 Go to publication entry in University of Southern Denmark's Research Portal Terms of use This work is brought to you by the University of Southern Denmark. Unless otherwise specified it has been shared according to the terms for self-archiving. If no other license is stated, these terms apply: • You may download this work for personal use only. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying this open access version If you believe that this document breaches copyright please contact us providing details and we will investigate your claim. Please direct all enquiries to [email protected] Download date: 28. Sep. 2021 1 180 R K Støving Anorexia nervosa and 180:1 R9–R27 Review endocrinology MECHANISMS IN ENDOCRINOLOGY Anorexia nervosa and endocrinology: a clinical update René Klinkby Støving1,2,3 Correspondence 1Nutrition Clinic, Center for Eating Disorders, Odense University Hospital, 2Endocrine Elite Research Centre, Institute should be addressed of Clinical Research, University of South Denmark, Faculty of Health Sciences, and 3Psychiatric Services in the Region to R K Støving of Southern Denmark, Odense, Denmark Email [email protected] Abstract Anorexia nervosa is a syndrome, that is collections of symptoms, which is not defined by its etiology.
    [Show full text]
  • Supplemental Table
    Supplementary Information DMD-AR-2020-000131 Evaluation of the disconnect between hepatocyte and microsome intrinsic clearance and in vitro in vivo extrapolation performance. Beth Williamson, Stephanie Harlfinger, Dermot F McGinnity Drug Metabolism and Pharmacokinetics, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK. Table S1. Compound physicochemical properties and in vitro ADME data. ACD ACD ACD Human Hep CLint Human Mic CLint Human Main Name MW Ion Class HBD HBA TPSA LogD 6 fuinc pKa A1 pKa B1 LogP (µL/min/x10 ) (µL/min/mg) fup isoform Chlorpromazine 318.9 Base 2 32 9.6 3.4 5.4 20 39 0.060 0.026 CYP2D6 Prochlorperazine 374.0 Base 3 35 7.7 3.6 4.8 12 2 0.023 0.141 CYP2D6 Dipyridamole 504.6 Neutral 4 12 145 6.5 3.8 0.3 28 96 0.407 0.048 UGT Erlotinib 393.4 Neutral 1 7 75 5.5 3.3 3.0 5 20 0.504 0.052 CYP3A Promethazine 284.4 Base 2 32 9.1 2.8 4.6 9 1 0.144 0.090 CYP2D6 Propranolol 259.4 Base 2 3 41 9.5 1.3 3.3 10 29 0.467 0.243 CYP2D6 Rosiglitazone 357.4 Neutral 1 5 97 6.3 6.5 2.5 2.8 13 37 0.514 0.003 Other Ondansetron 293.4 Base 4 40 6.8 1.6 2.8 3 8 0.842 0.435 CYP3A Amsacrine 393.5 Neutral 2 5 89 8.2 3.1 3.2 11 40 0.434 0.007 CYP1A Antazoline 265.4 Base 1 3 28 10.3 1.4 3.6 52 195 0.726 0.562 CYP3A Gefitinib 446.9 Base 1 7 69 7.0 3.7 3.7 4 44 0.214 0.035 CYP3A Edaravone 174.2 Neutral 1 3 33 2.7 0.5 1.1 2 65 0.828 0.001 UGT Semaxanib 238.3 Neutral 2 2 45 13.2 1.5 3.4 3.0 28 68 0.036 0.031 CYP3A Verapamil 454.6 Base 6 64 8.1 2.6 4.0 23 180 0.548 0.155 CYP3A Imatinib 493.6 Base 2 7 86 13.3 7.6 2.5 3.1 3 35 0.405
    [Show full text]
  • 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.
    [Show full text]
  • Disposal of Solid Chemicals in the Normal Trash
    Disposal of Solid Chemicals in the Normal Trash Many solid chemicals can be safety discarded into the normal trash, provided they are in containers that are not broken or cracked and have tightly fitting caps. These chemicals are considered acceptable for ordinary disposal because they display none of the properties of hazardous waste, are of low acute toxicity, and have not been identified as having any chronic toxic effects as summarized in the National Institute of Occupational Safety and Health (NIOSH) “Registry of Toxic Effects of Chemical Substances”. Examples of chemicals acceptable for disposal as regular trash are listed below. To dispose of these chemicals, place the containers in a box lined with a plastic bag, tape the top of the box shut, write “Normal Trash” on the box and then place the box next to the lab trash container. Only solid forms of these chemicals can be disposed in this manner. Any questions about these chemicals or other chemicals that may be disposed of in the normal trash should be directed to the Hazardous Materials Technician (610) 330-5225. Chemicals Generally Acceptable for Disposal as Regular Trash Acacia powder, gum Detergent (most) Methyl salicylate Sodium carbonate arabic Cation exchange resins Methylene blue Sodium chloride Acid, Ascorbic Chromatographic Methyl stearate Sodium citrate Acid, Benzoic absorbents Nutrient agar Sodium dodecyl sulfate Acid, Boric Crystal violet Octacosane (SDS) Acid, Casamind Dextrin Parafin Sodium formate Acid, Citric Dextrose Pepsin Sodium iodide Acid, Lactic Diatomaceous
    [Show full text]
  • Dietary Supplements Compendium Volume 1
    2015 Dietary Supplements Compendium DSC Volume 1 General Notices and Requirements USP–NF General Chapters USP–NF Dietary Supplement Monographs USP–NF Excipient Monographs FCC General Provisions FCC Monographs FCC Identity Standards FCC Appendices Reagents, Indicators, and Solutions Reference Tables DSC217M_DSCVol1_Title_2015-01_V3.indd 1 2/2/15 12:18 PM 2 Notice and Warning Concerning U.S. Patent or Trademark Rights The inclusion in the USP Dietary Supplements Compendium of a monograph on any dietary supplement in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grant of, or authority to exercise, any right or privilege protected by such patent or trademark. All such rights and privileges are vested in the patent or trademark owner, and no other person may exercise the same without express permission, authority, or license secured from such patent or trademark owner. Concerning Use of the USP Dietary Supplements Compendium Attention is called to the fact that USP Dietary Supplements Compendium text is fully copyrighted. Authors and others wishing to use portions of the text should request permission to do so from the Legal Department of the United States Pharmacopeial Convention. Copyright © 2015 The United States Pharmacopeial Convention ISBN: 978-1-936424-41-2 12601 Twinbrook Parkway, Rockville, MD 20852 All rights reserved. DSC Contents iii Contents USP Dietary Supplements Compendium Volume 1 Volume 2 Members . v. Preface . v Mission and Preface . 1 Dietary Supplements Admission Evaluations . 1. General Notices and Requirements . 9 USP Dietary Supplement Verification Program . .205 USP–NF General Chapters . 25 Dietary Supplements Regulatory USP–NF Dietary Supplement Monographs .
    [Show full text]
  • Molecular Medicine Tri-Conference
    Register by January 15 and SAVE up to $200 Premier Sponsors Corporate Sponsors Conference: February 3-5 | Exhibits: February 3-4 Moscone North Convention Center | San Francisco, CA PLENARY KEYNOTES When Drug Research is Personal John F. Crowley, Founder, Novazyme Pharmaceuti cals, Inc. Technology, Aging, and the Brain Biotechnologies GmbH ® Gary W. Small, M.D., Professor, Meso Scale Discovery David Geff en School of Medicine, University of California, Los Angeles Chips, Clones and Living Beyond 100 Paul J.H. Schoemaker, Ph.D., Lead Sponsoring Publicati ons M.B.A., Professor, Wharton School of Business Corporate Support Sponsors Co - Sponsors The State of California Cambridge Healthtech Institute • 250 First Avenue, Suite 300, Needham, MA 02494 Telephone: 781-972-5400 or Toll-Free in the U.S. 888-999-6288 • Fax: 781-972-5425 Tri-Conference.com Media Partners CONFERENCE-AT-A-GLANCE Tuesday, February 2 The Open Access Publisher 8:00 AM Morning Short Course Registration and Coffee 9:00 - 12:00 PM Morning Short Courses (Courses 1-6) 10:15 - 10:30 Networking Coffee Break 1:00 - 2:00 Afternoon Short Course Registration 2:00 - 5:00 Afternoon Short Courses (Courses 7-12) 3:15 - 3:30 Networking Refreshment Break 5:00 Close of Day Wednesday, February 3 7:00 AM Registration and Morning Coffee 8:00 - 9:40 Plenary Keynotes 9:40 - 11:00 Grand Opening Refreshment Break in the Exhibit Hall Nanomedicine 11:00 - 12:40 PM Concurrent Channels 12:40 - 1:45 Sponsored Luncheon Presentations or Lunch on Your Own 1:45 - 2:15 Dessert in the Exhibit Hall 2:15 - 4:20
    [Show full text]