TAG Mail – 26 August 2021 COVID-19 RESOURCES & ARTICLES of INTEREST Please Click This Link for the Cumulative Listing of COVID-19 Resources in Past TAG Mails
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Stanford Chem-H Presentation (PDF)
KiNativ® In situ kinase profiling Stanford University ChEM-H confidential @KiNativPlatform Principle of the KiNativ platform • ATP (or ADP) acyl phosphate binds to, and covalently modifies Lysine residues in the active site • Thus, ATP acyl phosphate with a desthiobiotin tag can be used capture and quantitate kinases in a complex lysate Acyl phosphate Desthiobiotin tag ATP 2 ATP acyl phosphate probe covalently modifies kinase in the active site Lysine 2 Lysine 1 3 ATP acyl phosphate probe covalently modifies kinase in the active site Lysine 2 Lysine 1 4 Samples trypsinized, probe-labeled peptides captured with streptavidin, and analyzed by targeted LC-MS2 Identification Quantitation Explicit determination of peptide Integration of signal from MS2 sequence and probe modification site fragment ions from MS2 spectrum 5 Comprehensive Coverage of Protein and Lipid Kinases Protein kinases Atypical kinases Green: Kinases detected on KiNativ Red: Kinases not detected on KiNativ ~80% of known protein and atypical kinases identified on the platform http://www.kinativ.com/coverage/protein-lipid.html 6 Profiling compound(s) on the KiNativ platform Control sample – add probe Sample: Lysate derived from any cell line or tissue from ANY species Treated sample – add inhibitor followed by probe Inhibited kinase Green: Kinases Blue: Probe Gray: Non-kinases Red: Inhibitor 7 Profiling compound(s) on the KiNativ platform Control sample – add probe MS signalMS Sample: Lysate derived from any cell line or tissue from ANY species Treated sample – add inhibitor -
Zuranolone | Medchemexpress
Inhibitors Product Data Sheet Zuranolone • Agonists Cat. No.: HY-103040 CAS No.: 1632051-40-1 Molecular Formula: C₂₅H₃₅N₃O₂ • Molecular Weight: 409.56 Screening Libraries Target: GABA Receptor Pathway: Membrane Transporter/Ion Channel; Neuronal Signaling Storage: Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month SOLVENT & SOLUBILITY In Vitro DMSO : 100 mg/mL (244.16 mM; Need ultrasonic) H2O : < 0.1 mg/mL (insoluble) Mass Solvent 1 mg 5 mg 10 mg Concentration Preparing 1 mM 2.4416 mL 12.2082 mL 24.4164 mL Stock Solutions 5 mM 0.4883 mL 2.4416 mL 4.8833 mL 10 mM 0.2442 mL 1.2208 mL 2.4416 mL Please refer to the solubility information to select the appropriate solvent. In Vivo 1. Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline Solubility: 2.5 mg/mL (6.10 mM); Suspended solution; Need ultrasonic 2. Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (6.10 mM); Clear solution 3. Add each solvent one by one: 10% DMSO >> 90% corn oil Solubility: ≥ 2.5 mg/mL (6.10 mM); Clear solution 4. Add each solvent one by one: 5% DMSO >> 40% PEG300 >> 5% Tween-80 >> 50% saline Solubility: 2.5 mg/mL (6.10 mM); Suspended solution; Need ultrasonic 5. Add each solvent one by one: 5% DMSO >> 95% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (6.10 mM); Clear solution BIOLOGICAL ACTIVITY Description Zuranolone is an orally active and potent neuroactive steroid positive allosteric modulator of GABAA receptor, with EC50s of [1] 296 and 163 nM for α1β2γ2 and α4β3δ GABAA receptors, respectively . -
Emergency Use Authorization (EUA) for Sotrovimab 500 Mg Center for Drug Evaluation and Research (CDER) Review
Emergency Use Authorization (EUA) for Sotrovimab 500 mg Center for Drug Evaluation and Research (CDER) Review Identifying Information Application Type EUA (EUA or Pre-EUA) If EUA, designate whether pre-event or intra-event EUA request. EUA Application EUA 000100 Number(s) Sponsor (entity EUA Sponsor requesting EUA or GlaxoSmithKline Research & Development Limited pre-EUA 980 Great West Road consideration), point Brentford Middlesex, TW8 9GS of contact, address, UK phone number, fax number, email GSK US Point of Contact address Debra H. Lake, M.S. Sr. Director Global Regulatory Affairs GlaxoSmithKline 5 Moore Drive PO Box 13398 Research Triangle Park, NC 27709-3398 (b) (6) Email: Phone Manufacturer, if GlaxoSmithKline, Parma. different from Sponsor Submission Date(s) Part 1: March 24, 2021 Part 2: March 29, 2021 Receipt Date(s) Part 1: March 24, 2021 Part 2: March 29, 2021 OND Division / Office Division of Antivirals /Office of Infectious Disease 1 Reference ID: 4802027 Product in the No Strategic National Stockpile (SNS) Distributor, if other (b) (4) than Sponsor I. EUA Determination/Declaration On February 4, 2020, the Secretary of Health and Human Services determined pursuant to section 564 of the Federal Food, Drug and Cosmetic (FD&C) Act that there is a public health emergency that has a significant potential to affect national security or the health and security of United States (US) citizens living abroad and that involves a novel (new) coronavirus (nCoV) first detected in Wuhan City, Hubei Province, China in 2019 (2019-nCoV). The virus is now named SARS-CoV-2, which causes the illness COVID-19. -
Sílvia Vilares Conde
Sílvia Vilares Conde FUNCTIONAL SIGNIFICANCE OF ADENOSINE IN CAROTID BODY CHEMOSENSORY ACTIVITY IN CONTROL AND CHRONICALLY HYPOXIC ANIMALS Lisboa, 2007 a Dissertation presented to obtain the PhD degree in “Ciências da Vida – Especialidade Farmacologia” at the Faculdade de Ciências Médicas, Universidade Nova de Lisboa and Biotecnología: Aplicaciones Biomédicas at the Facultad de Medicina, Universidad de Valladolid Supervised by Profs. Constancio Gonzalez, Emília Monteiro and Ana Obeso. b Realizado com o apoio da Fundação para a Ciência e Tecnologia, SFRH/BD/14178/2003 financiada pelo POCI 2010 no âmbito da Formação avançada para a Ciência, Medida IV.3. c To my mum and dad d This work: Originated the following publications: - Conde S.V., Obeso A., Vicario I., Rigual R., Rocher A. and Gonzalez C. (2006), Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors, J. Neurochem., 98, 616-628. (Chapter 3) - Conde S.V. and Monteiro E.C. (2006), Activation of nicotinic ACh receptors with α4 subunits induces adenosine release at the rat carotid body, Br. J. Pharmacol., 147, 783-789. (Chapter 2) - Conde S.V. and Monteiro E.C. (2004), Hypoxia induces adenosine release from the rat carotid body, J. Neurochem., 89 (5), 1148-1156. (Chapter 1) - Conde S.V. and Monteiro E.C. (2003), Adenosine-acetylcholine interactions at the rat carotid body, In: “Chemoreception: From cellular signalling to functional plasticity”, JM Pequinot et al. (Eds), Klumer Academic Press London, 305-311. (Chapter 2) Won the following awards: - 1st Prize “De Castro-Heymans–Neil Award” awarded by ISAC (International Society for Arterial Chemoreception) to the best work presented by a Young Researcher each triennial ISAC Meeting, 2002 - Pfizer Honor Young Researcher Prize awarded by the Portuguese Society of Medical Sciences, 2002 e Functional significance of adenosine in carotid body chemoreception PhD thesis, Silvia Vilares Conde INDEX Page List of Figures and Tables……………………………………………………….. -
Physiology-2021-Abstract-Book.Pdf (Physoc.Org)
Physiology 2021 Our Annual Conference 12 – 16 July 2021 Online | Worldwide #Physiology2021 Contents Prize Lectures 1 Symposia 7 Oral Communications 63 Poster Communications 195 Abstracts Experiments on animals and animal tissues It is a requirement of The Society that all vertebrates (and Octopus vulgaris) used in experiments are humanely treated and, where relevant, humanely killed. To this end authors must tick the appropriate box to confirm that: For work conducted in the UK, all procedures accorded with current UK legislation. For work conducted elsewhere, all procedures accorded with current national legislation/guidelines or, in their absence, with current local guidelines. Experiments on humans or human tissue Authors must tick the appropriate box to confirm that: All procedures accorded with the ethical standards of the relevant national, institutional or other body responsible for human research and experimentation, and with the principles of the World Medical Association’s Declaration of Helsinki. Guidelines on the Submission and Presentation of Abstracts Please note, to constitute an acceptable abstract, The Society requires the following ethical criteria to be met. To be acceptable for publication, experiments on living vertebrates and Octopus vulgaris must conform with the ethical requirements of The Society regarding relevant authorisation, as indicated in Step 2 of submission. Abstracts of Communications or Demonstrations must state the type of animal used (common name or genus, including man. Where applicable, abstracts must specify the anaesthetics used, and their doses and route of administration, for all experimental procedures (including preparative surgery, e.g. ovariectomy, decerebration, etc.). For experiments involving neuromuscular blockade, the abstract must give the type and dose, plus the methods used to monitor the adequacy of anaesthesia during blockade (or refer to a paper with these details). -
JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors
Drugs https://doi.org/10.1007/s40265-020-01261-8 CURRENT OPINION JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors Miguel Nogueira1 · Luis Puig2 · Tiago Torres1,3 © Springer Nature Switzerland AG 2020 Abstract Despite advances in the treatment of psoriasis, there is an unmet need for efective and safe oral treatments. The Janus Kinase– Signal Transducer and Activator of Transcription (JAK–STAT) pathway plays a signifcant role in intracellular signalling of cytokines of numerous cellular processes, important in both normal and pathological states of immune-mediated infamma- tory diseases. Particularly in psoriasis, where the interleukin (IL)-23/IL-17 axis is currently considered the crucial pathogenic pathway, blocking the JAK–STAT pathway with small molecules would be expected to be clinically efective. However, relative non-specifcity and low therapeutic index of the available JAK inhibitors have delayed their integration into the therapeutic armamentarium of psoriasis. Current research appears to be focused on Tyrosine kinase 2 (TYK2), the frst described member of the JAK family. Data from the Phase II trial of BMS-986165—a selective TYK2 inhibitor—in psoriasis have been published and clinical results are encouraging, with a large Phase III programme ongoing. Further, the selective TYK2 inhibitor PF-06826647 is being tested in moderate-to-severe psoriasis in a Phase II clinical trial. Brepocitinib, a potent TYK2/JAK1 inhibitor, is also being evaluated, as both oral and topical treatment. Results of studies with TYK2 inhibitors will be important in assessing the clinical efcacy and safety of these drugs and their place in the therapeutic armamentarium of psoriasis. -
(19) United States (12) Patent Application Publication (10) Pub
US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist. -
Stem Cell/Wnt
Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Stem Cell/Wnt Stem cells are required for continuous tissue maintenance within diverse organs, stem cell activity is often externally dictated by the microenvironment (the niche) so that stem cell output is precisely shaped to meet homeostatic needs or regenerative demands. Several key signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the JAK/STAT, Hedgehog, Wnt, Notch, Smad, PI3K/phosphatase and tensin homolog, and NK-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Recent studies mainly focus on cancer stem cell, induced pluripotent stem cell, neural stem cell and maintenance of embryonic stem cell pluripotency. Cancer stem cells (CSCs) have been believed to be responsible for tumor initiation, growth, and recurrence. Numerous agents have been developed to specifically target CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2, and c-Myc and transcription of GLI. Induced pluripotent stem cells (iPSCs) have the capacity to differentiate into various types of cells, and a self-renewing resource, and scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Novel pathological mechanisms have been elucidated, new drugs originating from iPSC screens are in the pipeline and the first clinical trial using human iPSC-derived products has been initiated. References: [1] Clevers H, et al. Science. 2014 Oct 3;346(6205):1248012. [2] Matsui WH. Medicine (Baltimore). -
Réponse Rapide
2021-05-17 13:58 17 mai 2021 Réponse en continu COVID-19 et biothérapies dirigées contre l’interleukine 6 ou son récepteur Une production de l’Institut national d’excellence en santé et en services sociaux (INESSS) 2021-05-17 13:58 Cette réponse a été préparée par les professionnels scientifiques de la Direction de l’évaluation et de la pertinence des modes d’intervention en santé et la Direction et de la Direction de l’évaluation des médicaments et des technologies à des fins de remboursement de l’Institut national d’excellence en santé et en services sociaux (INESSS). RESPONSABILITÉ L’INESSS assume l’entière responsabilité de la forme et du contenu définitif de ce document au moment de sa publication. Les positions qu’il contient ne reflètent pas forcément les opinions des personnes consultées aux fins de son élaboration. MISE À JOUR Suivant l’évolution de la situation, les conclusions de cette réponse mise à jour pourraient être appelées à changer. Dépôt légal Bibliothèque et Archives nationales du Québec, 2021 Bibliothèque et Archives Canada, 2021 ISBN 978-2-550-86479-0 (PDF) © Gouvernement du Québec, 2021 La reproduction totale ou partielle de ce document est autorisée à condition que la source soit mentionnée. Pour citer ce document : Institut national d’excellence en santé et en services sociaux (INESSS). COVID-19 et biothérapies dirigées contre l’interleukine 6 ou son récepteur. Québec, Qc : INESSS; 2021. 123 p. L’Institut remercie les membres de son personnel qui ont contribué à l’élaboration du présent document. 2 2021-05-17 13:58 COVID-19 et biothérapies dirigées contre l’interleukine 6 ou son récepteur Le présent document ainsi que les constats qu’il énonce ont été rédigés en réponse à une interpellation du ministère de la Santé et des Services sociaux dans le contexte de la crise sanitaire liée à la maladie à coronavirus (COVID-19) au Québec. -
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. -
Studies on New Pharmacological Treatments for Alcohol Dependence - and the Importance of Objective Markers of Alcohol Consumption
Studies on new pharmacological treatments for alcohol dependence - and the importance of objective markers of alcohol consumption Andrea de Bejczy 2016 Addiction Biology Unit Section of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at University of Gothenburg Sweden Cover illustration: by A. de Bejczy Inspired by Stan Lee’s “The Invincible Ironman. The empty shell”, Marvel Comics “…HIS VOICE IS HOARSE, HIS HAND TREMBLING AS HE REACHES FOR THE GLEAMING OBJECT THAT SEEMS BOTH WONDERFUL AND TERRIBLE TO HIM…” Studies on new pharmacological treatments for alcohol dependence ©Andrea de Bejczy [email protected] ISBN: 978-91-628-9788-8 (printed publication) ISBN: 978-91-628-9789-5 (e-publication) http://hdl.handle.net/2077/42349 Printed in Gothenburg, Sweden 2016 By INEKO ii La familia iii iv Studies on new pharmacological treatments for alcohol dependence - and the importance of objective markers of alcohol consumption Andrea de Bejczy Addiction Biology Unit Section of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at University of Gothenburg ABSTRACT This thesis will guide you through three randomized controlled trials (RCT) on three pharmacotherapies for alcohol dependence; the antidepressant drug mirtazapine, the smoking cessation drug varenicline and the glycine-uptake inhibitor Org 25935. The mirtazapine study was an investigator initiated single- center harm-reduction study with alcohol consumption measured by self-report in a diary as main outcome. The results indicated that mirtazapine reduced alcohol consumption in males with heredity for alcohol use disorder (AUD). The Org 25935 study was an international multi-center study with abstinence as treatment goal, main time to relapse and alcohol consumption was measured by self-report collected by the Time Line Follow Back method (TLFB). -
Evidence-Based Guidelines for the Pharmacological Management of Substance Abuse, Harmful Use, Addictio
444324 JOP0010.1177/0269881112444324Lingford-Hughes et al.Journal of Psychopharmacology 2012 BAP Guidelines BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, Journal of Psychopharmacology 0(0) 1 –54 harmful use, addiction and comorbidity: © The Author(s) 2012 Reprints and permission: sagepub.co.uk/journalsPermissions.nav recommendations from BAP DOI: 10.1177/0269881112444324 jop.sagepub.com AR Lingford-Hughes1, S Welch2, L Peters3 and DJ Nutt 1 With expert reviewers (in alphabetical order): Ball D, Buntwal N, Chick J, Crome I, Daly C, Dar K, Day E, Duka T, Finch E, Law F, Marshall EJ, Munafo M, Myles J, Porter S, Raistrick D, Reed LJ, Reid A, Sell L, Sinclair J, Tyrer P, West R, Williams T, Winstock A Abstract The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people. Keywords Substance misuse, addiction, guidelines, pharmacotherapy, comorbidity Introduction guidelines (e.g.