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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 . -
Mrna Vaccine: a Potential Therapeutic Strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei*
Wang et al. Molecular Cancer (2021) 20:33 https://doi.org/10.1186/s12943-021-01311-z REVIEW Open Access mRNA vaccine: a potential therapeutic strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei* Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases. Keywords: mRNA vaccine, Self-amplifying RNA, Non-replicating mRNA, Modification, Immunogenicity, Delivery strategy, COVID-19 mRNA vaccine, Clinical trials, Antibody-dependent enhancement, Dendritic cell targeting Introduction scientists are seeking to develop effective cancer vac- A vaccine stimulates the immune response of the body’s cines. -
A Review of COVID-19 Vaccines in Development: 6 Months Into the Pandemic
Article Review A review of COVID-19 vaccines in development: 6 months into the pandemic Merlin Sanicas, Melvin Sanicas, Doudou Diop, Emanuele Montomoli Corresponding author: Doudou Diop, PATH, Dakar, Sénégal. [email protected] Received: 13 Jul 2020 - Accepted: 29 Jul 2020 - Published: 05 Oct 2020 Keywords: Coronavirus, COVID-19, pandemic, vaccine development Copyright: Merlin Sanicas et al. Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cite this article: Merlin Sanicas et al. A review of COVID-19 vaccines in development: 6 months into the pandemic. Pan African Medical Journal. 2020;37(124). 10.11604/pamj.2020.37.124.24973 Available online at: https://www.panafrican-med-journal.com/content/article/37/124/full A review of COVID-19 vaccines in development: 6 Abstract months into the pandemic 1 2 3,& The advent of the COVID-19 pandemic and the Merlin Sanicas , Melvin Sanicas , Doudou Diop , dynamics of its spread is unprecedented. 4,5 Emanuele Montomoli Therefore, the need for a vaccine against the virus is huge. Researchers worldwide are working 1Centre de Recherche en Cancérologie de around the clock to find a vaccine. Experts Marseille, Université Aix-Marseille, Marseille, 2 estimate that a fast-tracked vaccine development France, Clinical Development, Takeda process could speed a successful candidate to Pharmaceuticals International AG, Zurich, 3 4 market in approximately 12-18 months. -
B-Cell Epitope Prediction for Peptide-Based Vaccine Design: Towards a Paradigm of Biological Outcomes for Global Health
Caoili et al. Immunome Research 2011, 7:2:2 http://www.immunome-research.net/ RESEARCH Open Access B-cell epitope prediction for peptide-based vaccine design: towards a paradigm of biological outcomes for global health Salvador Eugenio C. Caoili Abstract Global health must address a rapidly evolving burden of disease, hence the urgent need for versatile generic technologies exemplified by peptide-based vaccines. B-cell epitope prediction is crucial for designing such vaccines; yet this approach has thus far been largely unsuccessful, prompting further inquiry into the underly- ing reasons for its apparent inadequacy. Two major obstacles to the development of B-cell epitope prediction for peptide-based vaccine design are (1) the prevailing binary classification paradigm, which mandates the problematic dichotomization of continuous outcome variables, and (2) failure to explicitly model biological consequences of immunization that are relevant to practical considerations of safety and efficacy. The first obstacle is eliminated by redefining the predictive task as quantitative estimation of empirically observable biological effects of antibody-antigen binding, such that prediction is benchmarked using measures of corre- lation between continuous rather than dichotomous variables; but this alternative approach by itself fails to address the second obstacle even if benchmark data are selected to exclusively reflect functionally relevant cross-reactivity of antipeptide antibodies with protein antigens (as evidenced by antibody-modulated protein biological activity), particularly where only antibody-antigen binding is actually predicted as a surrogate for its biological effects. To overcome the second obstacle, the prerequisite is deliberate effort to predict, a priori, biological outcomes that are of immediate practical significance from the perspective of vaccination. -
Heterosubtypic Influenza Protection Elicited by Double-Layered
Heterosubtypic influenza protection elicited by double- layered polypeptide nanoparticles in mice Lei Denga, Timothy Z. Changb, Ye Wanga, Song Lib, Shelly Wangc, Shingo Matsuyamaa, Guoying Yud, Richard W. Compansc, Jian-Dong Lia, Mark R. Prausnitzb, Julie A. Championb, and Bao-Zhong Wanga,1 aCenter for Inflammation, Immunity & Infection, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303; bSchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332; cEmory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30307; and dState Key Laboratory of Fibrosis Biology, College of Life Science, Henan Normal University, Xinxiang, 453002 Henan, China Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved July 9, 2018 (received for review April 5, 2018) Influenza is a persistent threat to public health. Here we report required for complete protection against a lethal influenza A that double-layered peptide nanoparticles induced robust specific challenge (14). immunity and protected mice against heterosubtypic influenza A Nanotechnology provides a promising approach for the de- virus challenges. We fabricated the nanoparticles by desolvating a velopment of new generations of influenza vaccines. Physiolog- composite peptide of tandem copies of nucleoprotein epitopes into ically activated disassembling nanoparticles mimic the biophysical nanoparticles as cores and cross-linking another composite peptide of and biochemical cues of virions and initiate “danger” signals that four tandem copies of influenza matrix protein 2 ectodomain epitopes enhance the activation of innate immunity and elicit potent cellular to the core surfaces as a coating. Delivering the nanoparticles via dis- and humoral immune responses with minimal cytotoxicity (15). -
Plant-Made HIV Vaccines and Potential Candidates
Plant-made HIV vaccines and potential candidates Jocelyne Tremouillaux-Guiller1, Khaled Moustafa2, Kathleen Hefferon3, Goabaone Gaobotse4, and Abdullah Makhzoum4 1Faculty of Pharmaceutical Sciences, University François Rabelais, Tours, France. 2Arabic Science Archive – ArabiXiv (https://arabixiv.org). 3Department of Microbiology, Cornell University, USA. 4Department of Biological Sciences & Biotechnology, Botswana International University of Science & Technology, Botswana. Correspondence: [email protected]; [email protected] Highlights HIV/AIDS is a partially treatable but not completely curable pandemic disease. Major advances have been made to treat patients living with HIV/AIDS. Developing HIV vaccines is an ongoing endeavor and moves at an accelerated pace Plant molecular pharming is a valuable tool in HIV/AIDS vaccine research. Abstract Millions of people around the world suffer from heavy social and health burdens related to HIV/AIDS and its associated opportunistic infections. To reduce these burdens, preventive and therapeutic vaccines are required. Effective HIV vaccines have been under investigation for several decades using different animal models. Potential plant-made HIV vaccine candidates have also gained attention in the past few years. In addition to this, broadly neutralizing antibodies produced in plants which can target conserved viral epitopes and neutralize mutating HIV strains have been identified. Numerous epitopes of glycoproteins and capsid proteins of HIV-1 are a part of HIV therapy. Here, we discuss some recent findings aiming to produce anti-HIV-1 recombinant proteins in engineered plants for AIDS prophylactics and therapeutic treatments. Keywords: plant made pharmaceuticals; HIV vaccine; AIDS drug; plant molecular pharming/farming; multiepitopic HIV vaccine. 1 Introduction Acquired Immunodeficiency Syndrome (AIDS) is one of the greatest challenges to global public health today. -
Vaccination in Developing Countries: Problems, Challenges and Opportunities - T
GLOBAL PERSPECTIVES IN HEALTH - Vol. II - Vaccination in Developing Countries: Problems, Challenges and Opportunities - T. Pang VACCINATION IN DEVELOPING COUNTRIES: PROBLEMS, CHALLENGES, AND OPPORTUNITIES T. Pang Department of Research Policy and Cooperation, World Health Organization, Geneva, Switzerland Keywords: Developing countries, vaccination, immunization Contents 1. Introduction 2. Challenges to Improving Vaccination 3. Obstacles to Effective Vaccination 4. Solutions to Problems of Access and Coverage 5. Mechanisms: Cooperation Between Industrialized Nations and Developing Nations 6. Recent Initiatives—A Brighter Future? 6.1. The International Vaccine Institute 6.2. Global Alliance for Vaccines and Immunization 6.3. Millennium Vaccine Initiative 6.4. International AIDS Vaccine Initiative 6.5. Malaria Vaccine Initiative 7. Role of the World Health Organization 8. The Future Glossary Bibliography Biographical Sketch Summary Vaccines are the most inexpensive means of improving health and lowering morbidity and mortality caused by infectious diseases in the developing world. However, and in spite of significant advances in science and technology, the implementation of global vaccination coverage remains a pipe dream. Many obstacles and challenges remain, and imaginative and bold solutions are required. Recent initiatives based on international cooperation,UNESCO philanthropy, and goodwill – promise EOLSS a brighter future for those in need living in the developing world. 1. IntroductionSAMPLE CHAPTERS The eradication of smallpox and the imminent demise of polio are clear reminders of the power of vaccination in dealing with the scourge of communicable diseases in the developing world. The World Health Organization’s (WHO) Expanded Program for Immunization (EPI), which is focused on the six major diseases of childhood (diphtheria, pertussis, tetanus, polio, measles, and tuberculosis), succeeded in dramatically raising immunization coverage in developing countries from 5% in the 1970s to more than 80% of the birth cohort in the 1990s. -
HIV Envelope Antigen Valency on Peptide Nanofibers
www.nature.com/scientificreports OPEN HIV envelope antigen valency on peptide nanofbers modulates antibody magnitude and binding breadth Chelsea N. Fries1,9, Jui‑Lin Chen2,3,9, Maria L. Dennis3, Nicole L. Votaw1, Joshua Eudailey3, Brian E. Watts3, Kelly M. Hainline1, Derek W. Cain3, Richard Barfeld4, Cliburn Chan4, M. Anthony Moody3,5,6, Barton F. Haynes3,6, Kevin O. Saunders2,3,6,7, Sallie R. Permar2,3,5,6,8, Genevieve G. Fouda2,3,5* & Joel H. Collier1,6* A major challenge in developing an efective vaccine against HIV‑1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV‑1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial‑based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofber‑based immunogens bearing the HIV gp120 envelope glycoprotein. These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofbers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof‑of‑concept for a nanofber vaccine platform generating broad, high binding antibody responses against the HIV‑1 envelope glycoprotein. HIV-1/AIDS has been responsible for 30 million deaths since it became a global pandemic1. Despite decades of research, a vaccine against HIV-1 has remained elusive. -
Immunity Against Mucosal Pathogens?
What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens? This information is current as Igor M. Belyakov and Jeffrey D. Ahlers of October 3, 2021. J Immunol 2009; 183:6883-6892; ; doi: 10.4049/jimmunol.0901466 http://www.jimmunol.org/content/183/11/6883 Downloaded from References This article cites 92 articles, 38 of which you can access for free at: http://www.jimmunol.org/content/183/11/6883.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 3, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens? Igor M. Belyakov1* and Jeffrey D. Ahlers† The route of vaccination is important in influencing im- stream, although some microorganisms are limited to the de- mune responses at the initial site of pathogen invasion velopment of disease only at the site of initial mucosal invasion where protection is most effective. -
View Presentation
Investor Presentation June 2020 Safe Harbor Statement • The slides presented today and the accompanying oral presentations contain forward-looking statements, which may be identified by the use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “opportunity”, “goal”, “potential,” or “continue,” and other similar expressions. • Forward-looking statements in this presentation include statements regarding: our plans and expectations for ZULRESSO, including our revenue expectations and the factors that may impact revenues; our expectations as to the development and regulatory path forward and filing requirements for zuranolone; our development plans, goals and strategy for our product candidates and the potential results of our development efforts; the anticipated timing of clinical trial initiation and reporting of results, including our belief as to our ability to mitigate the possible impact of the COVID-19 pandemic on our clinical development timelines; the potential profile and benefit of our product candidates; our belief in the potential of our product candidates in various indications; the estimated number of patients with the disorders and diseases we are studying or plan to study; our financial expectations, including with respect to year-end cash; our belief that existing cash will support operations into 2022; and our expectations as to the goals, opportunity and potential for our business. • These forward-looking statements are neither promises -
Potential Applications for Mrna and Peptide-Based Vaccines
viruses Article An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines Guglielmo Lucchese 1,*,†, Hamid Reza Jahantigh 2,3,† , Leonarda De Benedictis 2, Piero Lovreglio 2 and Angela Stufano 2,3 1 Department of Neurology, Medical University of Greifswald, 17475 Greifswald, Germany 2 Interdisciplinary Department of Medicine-Section of Occupational Medicine, University of Bari, 70124 Bari, Italy; [email protected] (H.R.J.); [email protected] (L.D.B.); [email protected] (P.L.); [email protected] (A.S.) 3 Animal Health and Zoonosis Doctoral Program, Department of Veterinary Medicine, University of Bari, 70010 Bari, Italy * Correspondence: [email protected] † These authors contributed equally to the work. Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1) infection affects millions of individuals worldwide and can lead to severe leukemia, myelopathy/tropical spastic paraparesis, and numerous other disorders. Pursuing a safe and effective immunotherapeutic approach, we compared the viral polyprotein and the human proteome with a sliding window approach in order to identify oligopeptide sequences unique to the virus. The immunological relevance of the viral unique oligopeptides was assessed by searching them in the immune epitope database (IEDB). We found that Citation: Lucchese, G.; Jahantigh, HTLV-1 has 15 peptide stretches each consisting of uniquely viral non-human pentapeptides which H.R.; De Benedictis, L.; Lovreglio, P.; Stufano, A. An Epitope Platform for are ideal candidate for a safe and effective anti-HTLV-1 vaccine. Indeed, experimentally validated Safe and Effective HTLV-1 epitopes, as retrieved from the IEDB, contain peptide sequences also present in a vast number HTLV-1-Immunization: Potential of human proteins, thus potentially instituting the basis for cross-reactions. -
Zuranolone—An Investigational Oral Neuroactive Steroid and Positive
Expert Interview Psychiatric Disorders Zuranolone—An Investigational Oral Neuroactive Steroid and Positive Allosteric Modulator of GABA Type A Receptors for Postpartum Depression and Major Depressive Disorder Handan Gunduz-Bruce Sage Therapeutics, Inc., Cambridge, MA, USA Handan Gunduz-Bruce Handan Gunduz-Bruce is Senior Medical Director at Sage Therapeutics, Inc. and Assistant Clinical Professor of Psychiatry at Yale School of Medicine. She received her medical degree from the Istanbul Medical Faculty in 1991 and then completed her residency in psychiatry, followed by a fellowship in clinical neuroscience at the Long Island Jewish Medical Center of Albert Einstein College of Medicine. Earlier in her academic career, Dr. Gunduz-Bruce’s research focused on the longitudinal course and pharmacological treatment of schizophrenia. Her later research included pathophysiology studies of schizophrenia and depression with a focus on the N-methyl-D-aspartate (NMDA) receptor function and GABAergic mechanisms using electrophysiological, imaging and biomarker approaches. More recently, she received her MBA degree in Leadership in Healthcare from Yale School of Management. Since the beginning of her tenure at Sage Therapeutics, Dr. Gunduz-Bruce has contributed to the approval of ZULRESSOTM, the first pharmacological treatment for postpartum depression in adults, and continues to oversee the development of zuranolone, an investigational oral neuroactive steroid and positive allosteric modulator of GABAA receptors, for postpartum depression and major