Predicting Drug Responses by Propagating Interactions Through Text-Enhanced Drug-Gene Networks
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WO 2017/145013 Al 31 August 2017 (31.08.2017) 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 2017/145013 Al 31 August 2017 (31.08.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 498/04 (2006.01) A61K 31/5365 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 519/00 (2006.01) A61P 25/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/IB20 17/050844 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (22) International Filing Date: KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, 15 February 2017 (15.02.2017) MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (25) Filing Language: English RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, (26) Publication Language: English TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/298,657 23 February 2016 (23.02.2016) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: PFIZER INC. [US/US]; 235 East 42nd Street, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, New York, New York 10017 (US). -
Telmisartan Use in Rats with Preexisting Osteoporotics Bone
Life Sciences 237 (2019) 116890 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Telmisartan use in rats with preexisting osteoporotics bone disorders T increases bone microarchitecture alterations via PPARγ Antonio Marcos Birocalea, Antonio Ferreira de Melo Jr.b, Pollyana Peixotob, Phablo Wendell Costalonga Oliveirab, Leandro Dias Gonçalves Ruffonic, Liliam Masako Takayamad, Breno Valentim Nogueirae, Keico Okino Nonakac, ∗ Rosa Maria Rodrigues Pereirad, José Martins de Oliveira Jr.f, Nazaré Souza Bissolib, a Department of Health Integrated Education, Federal University of Espirito Santo, Vitória, ES, Brazil b Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil c Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, Brazil d Department of Medical Clinic, Medicine College, University of São Paulo, São Paulo, SP, Brazil e Department of Morphology, Federal University of Espirito Santo, Vitoria, ES, Brazil f Laboratory of Applied Nuclear Physics, University of Sorocaba, Sorocaba, SP, Brazil ARTICLE INFO ABSTRACT Keywords: Aims: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for Telmisartan to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of PPARγ telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and Hypertension lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impair- Ovariectomy ment has been demonstrated. Bone Main methods: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. -
PEMD-91-12BR Off-Label Drugs: Initial Results of a National Survey
11 1; -- __...._-----. ^.-- ______ -..._._ _.__ - _........ - t Ji Jo United States General Accounting Office Washington, D.C. 20648 Program Evaluation and Methodology Division B-242851 February 25,199l The Honorable Edward M. Kennedy Chairman, Committee on Labor and Human Resources United States Senate Dear Mr. Chairman: In September 1989, you asked us to conduct a study on reimbursement denials by health insurers for off-label drug use. As you know, the Food and Drug Administration designates the specific clinical indications for which a drug has been proven effective on a label insert for each approved drug, “Off-label” drug use occurs when physicians prescribe a drug for clinical indications other than those listed on the label. In response to your request, we surveyed a nationally representative sample of oncologists to determine: . the prevalence of off-label use of anticancer drugs by oncologists and how use varies by clinical, demographic, and geographic factors; l the extent to which third-party payers (for example, Medicare intermediaries, private health insurers) are denying payment for such use; and l whether the policies of third-party payers are influencing the treatment of cancer patients. We randomly selected 1,470 members of the American Society of Clinical Oncologists and sent them our survey in March 1990. The sam- pling was structured to ensure that our results would be generalizable both to the nation and to the 11 states with the largest number of oncologists. Our response rate was 56 percent, and a comparison of respondents to nonrespondents shows no noteworthy differences between the two groups. -
(12) Patent Application Publication (10) Pub. No.: US 2004/0224012 A1 Suvanprakorn Et Al
US 2004O224012A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0224012 A1 Suvanprakorn et al. (43) Pub. Date: Nov. 11, 2004 (54) TOPICAL APPLICATION AND METHODS Related U.S. Application Data FOR ADMINISTRATION OF ACTIVE AGENTS USING LIPOSOME MACRO-BEADS (63) Continuation-in-part of application No. 10/264,205, filed on Oct. 3, 2002. (76) Inventors: Pichit Suvanprakorn, Bangkok (TH); (60) Provisional application No. 60/327,643, filed on Oct. Tanusin Ploysangam, Bangkok (TH); 5, 2001. Lerson Tanasugarn, Bangkok (TH); Suwalee Chandrkrachang, Bangkok Publication Classification (TH); Nardo Zaias, Miami Beach, FL (US) (51) Int. CI.7. A61K 9/127; A61K 9/14 (52) U.S. Cl. ............................................ 424/450; 424/489 Correspondence Address: (57) ABSTRACT Eric G. Masamori 6520 Ridgewood Drive A topical application and methods for administration of Castro Valley, CA 94.552 (US) active agents encapsulated within non-permeable macro beads to enable a wider range of delivery vehicles, to provide longer product shelf-life, to allow multiple active (21) Appl. No.: 10/864,149 agents within the composition, to allow the controlled use of the active agents, to provide protected and designable release features and to provide visual inspection for damage (22) Filed: Jun. 9, 2004 and inconsistency. US 2004/0224012 A1 Nov. 11, 2004 TOPCAL APPLICATION AND METHODS FOR 0006 Various limitations on the shelf-life and use of ADMINISTRATION OF ACTIVE AGENTS USING liposome compounds exist due to the relatively fragile LPOSOME MACRO-BEADS nature of liposomes. Major problems encountered during liposome drug Storage in vesicular Suspension are the chemi CROSS REFERENCE TO OTHER cal alterations of the lipoSome compounds, Such as phos APPLICATIONS pholipids, cholesterols, ceramides, leading to potentially toxic degradation of the products, leakage of the drug from 0001) This application claims the benefit of U.S. -
Stimulatory Action of Telmisartan, an Antagonist of Angiotensin II Receptor, on Voltage-Gated Na+ Current: Experimental and Theoretical Studies
Chinese Journal of Physiology 61(1): 1-13, 2018 1 DOI: 10.4077/CJP.2018.BAG516 Stimulatory Action of Telmisartan, an Antagonist of Angiotensin II Receptor, on Voltage-Gated Na+ Current: Experimental and Theoretical Studies Tzu-Tung Chang, Chia-Jung Yang, Yu-Chi Lee, and Sheng-Nan Wu Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan, Republic of China Abstract Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this agent has any direct effects on ion currents remains unexplored. In whole-cell current recordings, addition of Tel + increased the peak amplitude of voltage-gated Na (NaV) current (INa) accompanied by the increased time constant of INa inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated INa in these cells is unlinked to either blockade of AT1R or activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). In order to explore how this compound affects the amplitude and kinetics of INa in neurons, a Hodgkin-Huxley-based (HH-based) model designed to mimic effect of Tel on the functional activities of neurons was computationally created in this study. In this framework, the parameter for h inactivation gating variable, which was changed in a stepwise fashion, was implemented + + to predict changes in membrane potentials (V) as a function of maximal Na (GNa), K conductance (GK), or both. As inactivation time course of INa was increased, the bifurcation point of V versus GNa became lower, and the range between subcritical and supercritical values at the bifurcation of V versus GK correspondingly became larger. -
REVIEW Peroxisome Proliferator-Activated Receptors In
199 REVIEW Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition P Froment, F Gizard1, D Defever2, B Staels1, J Dupont3 and P Monget3 INSERM U.418, UMR Communications Cellulaire et Différenciation, Hôpital Debrousse, 29 rue Soeur Bouvier, 69322 Lyon, France 1INSERM U.545, Institut Pasteur de Lille et Faculté de Pharmacie Université de Lille 2, 1 rue du Pr Calmette, 59019 Lille, France 2LMCB, Department of Molecular Biomedical Research, V.I.B., Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium 3Physiologie de la reproduction et des comportements, UMR 6175 INRA-CNRS-Université F. Rabelais de Tours-Haras Nationaux, 37380 Nouzilly, France (Requests for offprints should be addressed to P Froment; [email protected]) Abstract Peroxisome proliferator-activated receptors (PPAR, granulosa cell proliferation and steroidogenesis in vitro. All PPAR/ and PPAR) are a family of nuclear receptors these recent data raise new questions about the biologic that are activated by binding of natural ligands, such as actions of PPARs in reproduction and their use in polyunsaturated fatty acids or by synthetic ligands. Syn- therapeutic treatments of fertility troubles such as PCOS thetic molecules of the glitazone family, which bind to or endometriosis. In this review, we first describe the roles PPAR, are currently used to treat type II diabetes and of PPARs in different compartments of the reproductive also to attenuate the secondary clinical symptoms fre- axis (from male and female gametogenesis to parturition), quently associated with insulin resistance, including poly- with a focus on PPAR. Secondly, we discuss the possible cystic ovary syndrome (PCOS). PPARs are expressed molecular mechanisms underlying the effect of glitazones in different compartments of the reproductive system on PCOS. -
Metabolism and Pharmacokinetics in the Development of New Therapeutics for Cocaine and Opioid Abuse
University of Mississippi eGrove Electronic Theses and Dissertations Graduate School 2012 Metabolism And Pharmacokinetics In The Development Of New Therapeutics For Cocaine And Opioid Abuse Pradeep Kumar Vuppala University of Mississippi Follow this and additional works at: https://egrove.olemiss.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Vuppala, Pradeep Kumar, "Metabolism And Pharmacokinetics In The Development Of New Therapeutics For Cocaine And Opioid Abuse" (2012). Electronic Theses and Dissertations. 731. https://egrove.olemiss.edu/etd/731 This Dissertation is brought to you for free and open access by the Graduate School at eGrove. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of eGrove. For more information, please contact [email protected]. METABOLISM AND PHARMACOKINETICS IN THE DEVELOPMENT OF NEW THERAPEUTICS FOR COCAINE AND OPIOID ABUSE A Dissertation presented in partial fulfillment of requirements for the degree of Doctor of Philosophy in Pharmaceutical Sciences in the Department of Pharmaceutics The University of Mississippi by PRADEEP KUMAR VUPPALA April 2012 Copyright © 2012 by Pradeep Kumar Vuppala All rights reserved ABSTRACT Cocaine and opioid abuse are a major public health concern and the cause of significant morbidity and mortality worldwide. The development of effective medication for cocaine and opioid abuse is necessary to reduce the impact of this issue upon the individual and society. The pharmacologic treatment for drug abuse has been based on one of the following strategies: agonist substitution, antagonist treatment, or symptomatic treatment. This dissertation is focused on the role of metabolism and pharmacokinetics in the development of new pharmacotherapies, CM304 (sigma-1 receptor antagonist), mitragynine and 7-hydroxymitragynine (µ-opioid receptor agonists), for the treatment of drug abuse. -
Endocrine Disrupting Compounds and Prostate Cell Proliferation
Review Article Clinics in Oncology Published: 18 Oct, 2016 Endocrine Disrupting Compounds and Prostate Cell Proliferation Joubert Banjop Kharlyngdoh and Per-Erik Olsson* Department of Biology, Örebro University, Sweden Abstract Epidemiological, in vitro and animal studies have indicated that Endocrine Disrupting Compounds (EDCs) influence the normal growth and development of the prostate as well as development and progression of prostate cancer. This has been linked to an increased presence of environmental chemicals that interfere with hormonal signaling. Many of these effects appear to be associated with interferences with steroid hormone receptor signaling or by affecting steroidogenesis. Currently, there is abundant evidence from epidemiological studies linking pesticides and EDCs with elevated prostate cancer risk. Bisphenol-A, a known EDC, has been shown to promote induction of Prostate Specific Antigen (PSA), which is a biomarker for prostate cancer, in the LNCaP human prostate carcinoma cells, and to increase prostate carcinogenesis in animal models. Our research has focused on AR signaling and identification of novel androgenic and anti-androgenic EDCs. Using prostate cancer cell lines we have shown that the AR agonist, TBECH, and antagonist ATE, which is also a partial ART877A agonist, induce PSA expression. With the increasing presence of these EDCs in indoor and outdoor air, follows an increased risk of disturbed prostate development, regulation and function. Hence, identification of the contribution of EDCs to prostate cancer -
Management of Side Effects of Antipsychotics
Management of side effects of antipsychotics Oliver Freudenreich, MD, FACLP Co-Director, MGH Schizophrenia Program www.mghcme.org Disclosures I have the following relevant financial relationship with a commercial interest to disclose (recipient SELF; content SCHIZOPHRENIA): • Alkermes – Consultant honoraria (Advisory Board) • Avanir – Research grant (to institution) • Janssen – Research grant (to institution), consultant honoraria (Advisory Board) • Neurocrine – Consultant honoraria (Advisory Board) • Novartis – Consultant honoraria • Otsuka – Research grant (to institution) • Roche – Consultant honoraria • Saladax – Research grant (to institution) • Elsevier – Honoraria (medical editing) • Global Medical Education – Honoraria (CME speaker and content developer) • Medscape – Honoraria (CME speaker) • Wolters-Kluwer – Royalties (content developer) • UpToDate – Royalties, honoraria (content developer and editor) • American Psychiatric Association – Consultant honoraria (SMI Adviser) www.mghcme.org Outline • Antipsychotic side effect summary • Critical side effect management – NMS – Cardiac side effects – Gastrointestinal side effects – Clozapine black box warnings • Routine side effect management – Metabolic side effects – Motor side effects – Prolactin elevation • The man-in-the-arena algorithm www.mghcme.org Receptor profile and side effects • Alpha-1 – Hypotension: slow titration • Dopamine-2 – Dystonia: prophylactic anticholinergic – Akathisia, parkinsonism, tardive dyskinesia – Hyperprolactinemia • Histamine-1 – Sedation – Weight gain -
Research Publications by DISTINCTIONS Any Scientist of Pakistan in Last 10 Year and SERVICES Secretary General, the Chemical Society of Pakistan
CV and List of Publications PROF. DR. MUHAMMAD IQBAL CHOUDHARY (Hilal-e-Imtiaz, Sitara-e-Imtiaz, Tamgha-ei-Imtiaz) International Center for Chemical and Biological Sciences (H. E. J. Research Institute of Chemistry, Dr. Panjwani Center for Molecular Medicine and Drug Research) University of Karachi, Karachi-75270 Pakistan Tel: (92-21) 34824924, 34824925 Fax: 34819018, 34819019 E-mail: [email protected] Web Page: www.iccs.edu Biodata and List of Publications Pag No. 2 MUHAMMAD IQBAL CHOUDHARY (Hilal-e-Imtiaz, Sitara-e-Imtiaz, Tamgha-e-Imtiaz) D-131, Phase II, D. O. H. S., Malir Cant., Karachi-75270, Pakistan Ph.: 92-21-4901110 MAILING INTERNATIONAL CENTER FOR CHEMICAL AND BIOLOGICAL SCIENCES ADDRESS (H. E. J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research) University of Karachi Karachi-74270, Pakistan Tel: (92-21) 34824924-5 Fax: (92-21) 34819018-9 Email: [email protected] Web: www.iccs.edu DATE OF BIRTH September 11, 1959 (Karachi, Pakistan) EDUCATION Doctor of Science (D.Sc.) (University of Karachi ) 2005 Ph.D. (Organic Chemistry) 1987 H. E. J. Research Institute of Chemistry University of Karachi, Karachi-75270, Pakistan Thesis Title: "The Isolation and Structural Studies on Some Medicinal Plants of Pakistan, Buxus papillosa, Catharanthus roseus, and Cissampelos pareira." M.Sc. (Organic Chemistry) 1983 University of Karachi, Karachi-75270, Pakistan B.Sc. (Chemistry, Biochemistry, Botany) 1980 University of Karachi, Karachi-75270, Pakistan AWARDS & Declared as the top most scientist (Number 1) among 1,650 HONORS scientists of Pakistan in all disciplines / fields of science and technology (year 2012) by the Pakistan Council for Science and Technology (Ministry of Science and Technology), Pakistan. -
PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. -
Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.