Exploration of the Orthosteric/Allosteric Interface In
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
(12) United States Patent (10) Patent N0.: US 8,343,962 B2 Kisak Et Al
US008343962B2 (12) United States Patent (10) Patent N0.: US 8,343,962 B2 Kisak et al. (45) Date of Patent: *Jan. 1, 2013 (54) TOPICAL FORMULATION (58) Field of Classi?cation Search ............. .. 514/226.5, 514/334, 420, 557, 567 (75) Inventors: Edward T. Kisak, San Diego, CA (US); See application ?le fOr Complete Search history. John M. NeWsam, La Jolla, CA (US); _ Dominic King-Smith, San Diego, CA (56) References C‘ted (US); Pankaj Karande, Troy, NY (US); Samir Mitragotri, Goleta, CA (US) US' PATENT DOCUMENTS 5,602,183 A 2/1997 Martin et al. (73) Assignee: NuvoResearchOntano (CA) Inc., Mississagua, 6,328,979 2B1 12/2001 Yamashita et a1. 7,001,592 B1 2/2006 Traynor et a1. ( * ) Notice: Subject to any disclaimer, the term of this 7,795,309 B2 9/2010 Kisak eta1~ patent is extended or adjusted under 35 2002/0064524 A1 5/2002 Cevc U.S.C. 154(b) by 212 days. FOREIGN PATENT DOCUMENTS This patent is subject to a terminal dis- W0 WO 2005/009510 2/2005 claimer- OTHER PUBLICATIONS (21) APPI' NO‘, 12/848,792 International Search Report issued on Aug. 8, 2008 in application No. PCT/lB2007/0l983 (corresponding to US 7,795,309). _ Notice ofAlloWance issued on Apr. 29, 2010 by the Examiner in US. (22) Med Aug- 2’ 2010 Appl. No. 12/281,561 (US 7,795,309). _ _ _ Of?ce Action issued on Dec. 30, 2009 by the Examiner in US. Appl. (65) Prior Publication Data No, 12/281,561 (Us 7,795,309), Us 2011/0028460 A1 Feb‘ 3’ 2011 Primary Examiner * Raymond Henley, 111 Related U 5 Application Data (74) Attorney, Agent, or Firm * Foley & Lardner LLP (63) Continuation-in-part of application No. -
Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, but Not Compensatory Plasticity, of Neuromuscular Synapses
14942 • The Journal of Neuroscience, November 25, 2009 • 29(47):14942–14955 Development/Plasticity/Repair Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses Megan C. Wright,1 Srilatha Potluri,1 Xueyong Wang,2 Eva Dentcheva,1 Dinesh Gautam,3 Alan Tessler,1,4 Ju¨rgen Wess,3 Mark M. Rich,2 and Young-Jin Son1 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, 2Department of Neuroscience, Cell Biology, and Physiology, Wright State University, Dayton, Ohio 45435, 3Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, and 4Department of Neurology, Department of Veterans Affairs Hospital, Philadelphia, Pennsylvania 19104 Muscarinic acetylcholine receptors (mAChRs) modulate synaptic function, but whether they influence synaptic structure remains un- known. At neuromuscular junctions (NMJs), mAChRs have been implicated in compensatory sprouting of axon terminals in paralyzed or denervated muscles. Here we used pharmacological and genetic inhibition and localization studies of mAChR subtypes at mouse NMJs to demonstrate their roles in synaptic stability and growth but not in compensatory sprouting. M2 mAChRs were present solely in motor neurons,whereasM1 ,M3 ,andM5 mAChRswereassociatedwithSchwanncellsand/ormusclefibers.BlockadeofallfivemAChRsubtypes with atropine evoked pronounced effects, -
Muscarinic Acetylcholine Type 1 Receptor Activity Constrains Neurite Outgrowth by Inhibiting Microtubule Polymerization and Mito
fnins-12-00402 June 26, 2018 Time: 12:46 # 1 ORIGINAL RESEARCH published: 26 June 2018 doi: 10.3389/fnins.2018.00402 Muscarinic Acetylcholine Type 1 Receptor Activity Constrains Neurite Outgrowth by Inhibiting Microtubule Polymerization and Mitochondrial Trafficking in Adult Sensory Neurons Mohammad G. Sabbir1*, Nigel A. Calcutt2 and Paul Fernyhough1,3 1 Division of Neurodegenerative Disorders, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada, 2 Department of Pathology, University of California, San Diego, San Diego, CA, United States, 3 Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada The muscarinic acetylcholine type 1 receptor (M1R) is a metabotropic G protein-coupled Edited by: receptor. Knockout of M1R or exposure to selective or specific receptor antagonists Roberto Di Maio, elevates neurite outgrowth in adult sensory neurons and is therapeutic in diverse University of Pittsburgh, United States models of peripheral neuropathy. We tested the hypothesis that endogenous M1R Reviewed by: activation constrained neurite outgrowth via a negative impact on the cytoskeleton Roland Brandt, University of Osnabrück, Germany and subsequent mitochondrial trafficking. We overexpressed M1R in primary cultures Rick Dobrowsky, of adult rat sensory neurons and cell lines and studied the physiological and The University of Kansas, United States molecular consequences related to regulation of cytoskeletal/mitochondrial dynamics *Correspondence: and neurite outgrowth. In adult primary neurons, overexpression of M1R caused Mohammad G. Sabbir disruption of the tubulin, but not actin, cytoskeleton and significantly reduced neurite [email protected] outgrowth. Over-expression of a M1R-DREADD mutant comparatively increased neurite Specialty section: outgrowth suggesting that acetylcholine released from cultured neurons interacts This article was submitted to with M1R to suppress neurite outgrowth. -
WO 2017/177262 Al 19 October 2017 (19.10.2017) P O P C T
(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 2017/177262 Al 19 October 2017 (19.10.2017) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/198 (2006.01) A61P 27/02 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, A61K 31/375 (2006.01) A61P 27/10 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (21) International Application Number: KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, PCT/AU20 17/0503 10 MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (22) International Filing Date: NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 10 April 2017 (10.04.2017) 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, (25) Filing Language: English ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 2016901339 11 April 2016 ( 11.04.2016) AU GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: UNIVERSITY OF CANBERRA [AU/AU]; TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, University Drive, Bruce, Australian Capital Territory 2617 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (AU). -
Muscarinic Toxin 7 Signals Via Ca2+/Calmodulin-Dependent Protein Kinase Kinase Β to Augment Mitochondrial Function and Prevent Neurodegeneration
Molecular Neurobiology (2020) 57:2521–2538 https://doi.org/10.1007/s12035-020-01900-x Muscarinic Toxin 7 Signals Via Ca2+/Calmodulin-Dependent Protein Kinase Kinase β to Augment Mitochondrial Function and Prevent Neurodegeneration Ali Saleh1 & Mohammad Golam Sabbir1 & Mohamad-Reza Aghanoori1,2 & Darrell R. Smith1 & Subir K. Roy Chowdhury1 & Lori Tessler1 & Jennifer Brown1 & Eva Gedarevich3 & Markos Z. Kassahun3 & Katie Frizzi3 & Nigel A. Calcutt 3 & Paul Fernyhough1,2 Received: 9 January 2020 /Accepted: 9 March 2020 /Published online: 20 March 2020 # The Author(s) 2020 Abstract Mitochondrial dysfunction is implicated in a variety of neurodegenerative diseases of the nervous system. Peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α) is a regulator of mitochondrial function in multiple cell types. In sensory neurons, AMP-activated protein kinase (AMPK) augments PGC-1α activity and this pathway is depressed in diabetes leading to mitochondrial dysfunction and neurodegeneration. Antimuscarinic drugs targeting the muscarinic acetylcholine type 1 receptor (M1R) prevent/reverse neurodegeneration by inducing nerve regeneration in rodent models of diabetes and chemotherapy-induced peripheral neuropathy (CIPN). Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)isan upstream regulator of AMPK activity. We hypothesized that antimuscarinic drugs modulate CaMKKβ to enhance activity of AMPK, and PGC-1α, increase mitochondrial function and thus protect from neurodegeneration. We used the specific M1R antagonist muscarinic toxin 7 (MT7) to manipulate muscarinic signaling in the dorsal root ganglia (DRG) neurons of normal rats or rats with streptozotocin-induced diabetes. DRG neurons treated with MT7 (100 nM) or a selective muscarinic antagonist, pirenzepine (1 μM), for 24 h showed increased neurite outgrowth that was blocked by the CaMKK inhibitor STO-609 (1 μM) or short hairpin RNA to CaMKKβ. -
1: Gastro-Intestinal System
1 1: GASTRO-INTESTINAL SYSTEM Antacids .......................................................... 1 Stimulant laxatives ...................................46 Compound alginate products .................. 3 Docuate sodium .......................................49 Simeticone ................................................... 4 Lactulose ....................................................50 Antimuscarinics .......................................... 5 Macrogols (polyethylene glycols) ..........51 Glycopyrronium .......................................13 Magnesium salts ........................................53 Hyoscine butylbromide ...........................16 Rectal products for constipation ..........55 Hyoscine hydrobromide .........................19 Products for haemorrhoids .................56 Propantheline ............................................21 Pancreatin ...................................................58 Orphenadrine ...........................................23 Prokinetics ..................................................24 Quick Clinical Guides: H2-receptor antagonists .......................27 Death rattle (noisy rattling breathing) 12 Proton pump inhibitors ........................30 Opioid-induced constipation .................42 Loperamide ................................................35 Bowel management in paraplegia Laxatives ......................................................38 and tetraplegia .....................................44 Ispaghula (Psyllium husk) ........................45 ANTACIDS Indications: -
TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage . -
Venom Week 2012 4Th International Scientific Symposium on All Things Venomous
17th World Congress of the International Society on Toxinology Animal, Plant and Microbial Toxins & Venom Week 2012 4th International Scientific Symposium on All Things Venomous Honolulu, Hawaii, USA, July 8 – 13, 2012 1 Table of Contents Section Page Introduction 01 Scientific Organizing Committee 02 Local Organizing Committee / Sponsors / Co-Chairs 02 Welcome Messages 04 Governor’s Proclamation 08 Meeting Program 10 Sunday 13 Monday 15 Tuesday 20 Wednesday 26 Thursday 30 Friday 36 Poster Session I 41 Poster Session II 47 Supplemental program material 54 Additional Abstracts (#298 – #344) 61 International Society on Thrombosis & Haemostasis 99 2 Introduction Welcome to the 17th World Congress of the International Society on Toxinology (IST), held jointly with Venom Week 2012, 4th International Scientific Symposium on All Things Venomous, in Honolulu, Hawaii, USA, July 8 – 13, 2012. This is a supplement to the special issue of Toxicon. It contains the abstracts that were submitted too late for inclusion there, as well as a complete program agenda of the meeting, as well as other materials. At the time of this printing, we had 344 scientific abstracts scheduled for presentation and over 300 attendees from all over the planet. The World Congress of IST is held every three years, most recently in Recife, Brazil in March 2009. The IST World Congress is the primary international meeting bringing together scientists and physicians from around the world to discuss the most recent advances in the structure and function of natural toxins occurring in venomous animals, plants, or microorganisms, in medical, public health, and policy approaches to prevent or treat envenomations, and in the development of new toxin-derived drugs. -
Fluticasone Furoate and Vilanterol for the Treatment of Chronic Obstructive Pulmonary Disease
Expert Review of Respiratory Medicine ISSN: 1747-6348 (Print) 1747-6356 (Online) Journal homepage: http://www.tandfonline.com/loi/ierx20 Fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease Gaetano Caramori, Paolo Ruggeri, Paolo Casolari, Kian Fan Chung, Giuseppe Girbino & Ian M. Adcock To cite this article: Gaetano Caramori, Paolo Ruggeri, Paolo Casolari, Kian Fan Chung, Giuseppe Girbino & Ian M. Adcock (2017): Fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease, Expert Review of Respiratory Medicine, DOI: 10.1080/17476348.2017.1386564 To link to this article: http://dx.doi.org/10.1080/17476348.2017.1386564 Accepted author version posted online: 28 Sep 2017. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierx20 Download by: [Imperial College London Library] Date: 29 September 2017, At: 01:13 Publisher: Taylor & Francis Journal: Expert Review of Respiratory Medicine DOI: 10.1080/17476348.2017.1386564 Review Fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease Gaetano Caramori1*, Paolo Ruggeri1, Paolo Casolari2, Kian Fan Chung3, Giuseppe Girbino1, Ian M. Adcock3. 1Unità Operativa Complessa di Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF) Università degli Studi di Messina, Italy. 2Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria, Università di Ferrara, Ferrara, Italy. 3Airways Disease Section, National Heart and Lung Institute, Royal Brompton Hospital Biomedical Research Unit, Imperial College London, UK. -
Oregon Drug Use Review / Pharmacy & Therapeutics Committee
© Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program OHA Division of Medical Assistance Programs 500 Summer Street NE, E35; Salem, OR 97301-1079 Phone 503-947-5220 | Fax 503-947-1119 Oregon Drug Use Review / Pharmacy & Therapeutics Committee Thursday, January 25, 2018 1:00 - 5:00 PM Barbara Roberts Human Services Building 500 Summer St. NE Salem, OR 97301 MEETING AGENDA NOTE: Any agenda items discussed by the DUR/P&T Committee may result in changes to utilization control recommendations to the OHA. Timing, sequence and inclusion of agenda items presented to the Committee may change at the discretion of the OHA, P&T Committee and staff. The DUR/P&T Committee functions as the Rules Advisory Committee to the Oregon Health Plan for adoption into Oregon Administrative Rules 410-121-0030 & 410-121-0040 as required by 414.325(9). I. CALL TO ORDER 1:00 PM A. Roll Call & Introductions R. Citron (OSU) B. Roles and Responsibilities of Committee Members T. Douglass (OHA) C. Conflict of Interest Declaration R. Citron (OSU) D. Election of Chair & Vice Chair R. Citron (OSU) E. Department and Legislative Update T. Douglass (OHA) F. Approval of Agenda and Minutes II. CONSENT AGENDA TOPICS R. Citron (OSU) 1:25 PM A. Noctiva® (desmopressin) Abbreviated Drug Review B. Drugs for Asthma and COPD Literature Scan 1. Public Comment III. DUR NEW BUSINESS 1:30 PM A. Hepatitis C Direct-Acting Antivirals Policy Discussion R. Citron (OSU) 1. Prior Authorization Criteria A. Seaman (OHSU) 2. Treatment of Hepatitis C in People who Inject Drugs 3. -
RMP Buscopan Part 0 Preliminary Section
EU RISK MANAGEMENT PLAN FOR HYOSCINE BUTYLBROMIDE PRELIMINARY SECTION Active substance(s) (INN or common name) Hyoscine butylbromide Belladonna alkaloids, semisynthetic, quarternary Pharmaco-therapeutic group (ATC Code) ammonium compounds (ATC code A03BB01) Name of Marketing Authorization Holder or Applicant Boehringer Ingelheim Limited Medicinal product(s) to which this RMP refers Hyoscine butylbromide (BUSCOPAN) (tablet and ampoule) Product(s) concerned (brand name(s)) BUSCOPAN ® (tablet and ampoule) Data lock point (DLP) for current Risk Management Plan 01-JUN-2016 (RMP) Version number of the current RMP Version 2.1_CA Date of final sign-off Property of the Sanofi group - strictly confidential Page 1 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA Table 1 - RMP version to be assessed as part of this application RMP Version number Version 2.1_CA Data lock point for this RMP 01-JUN-2016 Date of final sign off Rationale for submitting an updated RMP Not applicable Summary of significant changes in this RMP Safety concerns: The important identified risk “Tachycardia in patients with cardiac risk factors (parenteral formulation)” was added. RMP: Risk Management Plan. Table 2 - Other RMP versions under evaluation RMP Version number Submitted on Submitted within Not applicable - - RMP: Risk Management Plan. Table 3 - Details of the currently approved RMP Version number 2.0 Approved with procedure - Date of approval (opinion date) - RMP: Risk Management -
Muscarinic, Adenosine and Tropomyosin-Related Kinase B Receptor Modulate the Neuromuscular Developmental Synapse Elimination Process
Muscarinic, adenosine and tropomyosin-related kinase B receptor modulate the neuromuscular developmental synapse elimination process Laura Nadal Magriñà ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs. ADVERTENCIA. El acceso a los contenidos de esta tesis doctoral y su utilización debe respetar los derechos de la persona autora. Puede ser utilizada para consulta o estudio personal, así como en actividades o materiales de investigación y docencia en los términos establecidos en el art. 32 del Texto Refundido de la Ley de Propiedad Intelectual (RDL 1/1996). Para otros usos se requiere la autorización previa y expresa de la persona autora. En cualquier caso, en la utilización de sus contenidos se deberá indicar de forma clara el nombre y apellidos de la persona autora y el título de la tesis doctoral.