DOCSLIB.ORG

Compositions for Treating Breast Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Compositions for Treating Breast Cancer (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 2018/148598 Al 16 August 2018 (16.08.2018) W !P O PCT (51) International Patent Classification: WARD, Carl, C. 1612 Buena Avenue, Berkeley, CA A61K 36/48 (2006.01) C07C 45/00 (2006.01) 94703 (US). A61K 36/484 (2006.01) C07C 45/41 (2006.01) (74) Agent: TERRANOVA, Zachary, L. et al; Mintz Levin A61P 35/00 (2006.01) C07C 45/45 (2006.01) Cohn Ferris Glovsky And Popeo, P.C., One Financial Cen (21) International Application Number: ter, Boston, MA 021 11 (US). PCT/US20 18/0 17702 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of national protection available): AE, AG, AL, AM, 09 February 2018 (09.02.2018) 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, DO, (25) Filing Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (26) Publication Language: English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (30) Priority Data: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/457,709 10 February 2017 (10.02.2017) US OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (71) Applicant: THE REGENTS OF THE UNIVERSITY OF SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, CALIFORNIA [US/US]; 1111 Franklin Street, Twelfth TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. Floor, Oakland, CA 94607-5200 (US). (84) Designated States (unless otherwise indicated, for every (72) Inventors: NOMURA, Daniel, K.; 4532 Davenport Av kind of regional protection available): ARIPO (BW, GH, enue, Berkeley, CA 94619 (US). ROBERTS, Lindsay, S.; GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, 337 S. Fremont St. #321, San Mateo, CA 94401 (US). UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (54) Title: COMPOSITIONS FOR TREATING BREAST CANCER 231 !VIFP cell survival > 0.01 0.1 1 10 100 licocha!cone (µ Μ) FIG. 5 (57) Abstract: Disclosed herein are compositions useful for inhibiting prostaglandin reductase 1(PTGRl ) activity. Further provided is a method of treating cancer, the method including administering to a subject in need thereof an effective amount of a PTGRl inhibitor. In another aspect is provided a method of treating triple negative breast cancer, the method including administering to a subject in need thereof an effective amount of a PTGRl inhibitor. In another aspect is provided a pharmaceutical composition including a PTGRl inhibitor and a pharmaceutically acceptable excipient. In preferred embodiments, the PTGRl inhibitor is a compound described herein. [Continued on nextpage] WO 2018/148598 Al llll II II 11III II I 11III II 11II I III II I II MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a)) COMPOSITIONS FOR TREATING BREAST CANCER CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 62/457,709, filed February 10, 2017, which is incorporated herein by reference in its entirety and for all purposes. REFERENCE TO A "SEQUENCE LISTING," A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED AS AN ASCII FILE [0002] The Sequence Listing written in file 052103-501001WO Sequence Listing_ST25.txt, created January 22, 2018, 4,768 bytes, machine format IBM-PC, MS Windows operating system, is hereby incorporated by reference. STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT [0003] This invention was made with government support under CA1 72667 awarded by the National Institutes of Health and under W81XWH-15-1-0050 awarded by the ARMY/MRMC. The government has certain rights in the invention. BACKGROUND [0004] In the United States, it is estimated that over 200,000 women will be diagnosed with breast cancer and nearly 40,000 women will die of breast cancer in 2016. Studies over the past decade have uncovered certain breast cancer cell-types, such as estrogen/progesterone/HER2 receptor (ER/PR/HER2)-negative (triple-negative) breast cancers (TNBCs) that show poor prognosis and chemotherapy-resistance within breast tumors. Eliminating these breast cancer types are critical in reducing the mortality associated with breast cancer. Disclosed herein, inter alia, are solutions to these and other problems in the art. BRIEF SUMMARY [0005] In an aspect is provided a compound having the formula: [0006] R is independently halogen, -CXS, -CHX^, -CH2X 1, -OCX^, - 1 D A B (0 A B (0 A B OCH2X , -OCHX , -CN, -SOniR , -SOviNR R , - H C ) R R , -N ) m i , - R R , (0 (0 (0 A B D A S0 D A (0 A (0)0 - C ) R , - C )-OR , - C ) R R , -OR , - R 2R , - R C ) R , - R C A R , - R 0 R , -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; two adjacent R substituents may optionally bejoined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol zl is an integer from 0 to 5. R 2 is 2 2 2 2 independently halogen, -CX , -CHX 2 , -CH 2 X , -OCX 3 , - 2 2 2D 2 A 2B (0 2 A 2 B (0) , 2 A 2 B OCH2X , -OCHX 2, -CN, -SO„2R , -SO 2 N R R , -NHC )NR R , -N m 2 -NR R , (0 2 (0 2 (0 2 A 2 B 2 D 2A S0 2 D 2 A (0 2 2 A (0)0 - C ) R , - C )-OR , - C )NR R , -OR , -NR 2R , -NR C ) R , -NR C 2 2 A 2 R , -NR O R , -N 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; two adjacent R 2 substituents may optionally bejoined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol z2 is an integer from 0 to 5. Each R A , R B , R , R D , R 2 A , R 2 B , R 2 , and R 2D is independently hydrogen, -CX 3 , -CN, -COOH, -CONH2, -CHX 2 , -CH 2 X , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R A and R B substituents bonded to the same nitrogen atom may optionally bejoined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 2 A and R 2 B substituents bonded to the same nitrogen atom may optionally bejoined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. Each X , X 1 , and X 2 is independently -F, -CI, -Br, or -I. The symbols nl and n2 are independently an integer from 0 to 4 . The symbols ml, m2, vl, and v2 are independently an integer from 1to 2 . [0007] In an aspect is provided a PTGR1 inhibitor. In embodiments, the PTGR1 inhibitor is a compound described herein. [0008] In an aspect is provided a method of treating cancer, the method including administering to a subject in need thereof an effective amount of a PTGRl inhibitor. In embodiments, the PTGRl inhibitor is a compound described herein. [0009] In an aspect is provided a method of treating triple negative breast cancer, the method including administering to a subject in need thereof an effective amount of a PTGRl inhibitor. In embodiments, the PTGRl inhibitor is a compound described herein. [0010] In an aspect is provided a method of treating cancer including administering to a subject in need thereof an effective amount of a compound described herein. [0011] In an aspect is provided a method of treating a disease associated with PTGRl activity including administering to a subject in need thereof an effective amount of a PTGRl inhibitor. [0012] In an aspect is provided a method of inhibiting PTGRl activity including contacting the PTGRl with a PTGRl inhibitor. [0013] In an aspect is provided a method of inhibiting PTGRl activity including contacting the PTGRl with a compound described herein. [0014] In an aspect is provided a PTGRl protein covalently bonded to a PTGRl inhibitor (a PTGRl protein-PTGRl inhibitor complex). [0015] In an aspect is provided a PTGRl protein covalently bonded to a compound described herein. BRIEF DESCRIPTION OF THE DRAWINGS [0016] FIGS. 1A-1C. Screening a library of drugs and drug candidates in TNBC cells. (FIGS. ΙΑ,ΙΒ) A library of drugs and drug candidates were screened in 231MFP and HCC38 TNBC cell lines for impairments in serum-free cell survival. (FIG. 1C) Cell survival of drugs and drug candidates that reproducibly and significantly impaired 231MFP, HCC38, and HCC70 viability by >50 % .
Load more

Recommended publications
  • WADA Technical Letter – TL07 ANDARINE
    WADA Technical Letter – TL07 Document Number: TL07 Version Number: 3.0 Written by: WADA Science Approved by: WADA Executive Committee Reviewed by: WADA Laboratory Expert Group Date: 21 December 2020 Effective Date: 1 January 2021 ANDARINE - FLUTAMIDE 1.0 Introduction WADA wishes to draw the attention of the Laboratories to the following observations and instructions on the analysis and reporting of SARM S4 (Andarine) Metabolites O-dephenylandarine and O- dephenylandarine glucuronide. The andarine Metabolites O-dephenylandarine and of O-dephenylandarine glucuronide may also be present in a Sample as a Metabolite of the anti-androgen Flutamide (Drogenil®, Eulexin®, Euflex®, Flutamin®, Flugere®), used primarily in the treatment of prostate cancer [1]. Since flutamide is not a Prohibited Substance in sports, the Laboratories shall not report an Adverse Analytical Finding (AAF) for andarine based on the monitoring of O-dephenylandarine [2]. Figure 1. Proposed metabolic pathway of flutamide and andarine (adapted from Perrenoud et al. [1]). 2.0 Analysis and Reporting Requirements Report the result as an AAF for andarine only when the presence of andarine (parent compound), and/or its glucuronic acid conjugate, and/or its deacetylated and/or hydroxylated Metabolites, and/or its bishydroxylated product [2] are confirmed in the Sample (regardless of the presence of flutamide and/or its Metabolite 2-hydroxyflutamide); [Comment: Laboratories shall not report an AAF for andarine based only on the presence of O- dephenylandarine.] 3.0 References [1] Perrenoud L. et al. Risk of false positive results to SARM S4 in case of therapeutic use of antineoplastic/antiandrogen drug containing flutamide: a case study.
    [Show full text]
  • Thesis Was Carried out at the K
    Experimental modeling and novel therapeutic strategies in melanoma brain metastasis Terje Sundstrøm Dissertation for the degree of philosophiae doctor (PhD) University of Bergen, Norway 2015 Dissertation date: June 9th 2015 LIST OF ABBREVIATIONS 3D 3-dimensional 5-ALA 5-aminolevulinic acid AAAS American Association for the Advancement of Science ACT Adoptive cell transfer ADC Apparent diffusion coefficient AJCC American Joint Committee on Cancer AKT Protein kinase B ALK Anaplastic lymphoma kinase APC Antigen-presenting cell APOE Apolipoprotein-E ATP Adenosine triphosphate B7-H3 B7 homolog 3 BBB Blood-brain barrier BCL2A1 Bcl-2-related protein A1 bFGF Basic fibroblast growth factor BLI Bioluminescence imaging BRAF Serine/threonine-protein kinase B-raf BRMS1 Breast cancer metastasis-suppressor 1 BTB Blood-tumor barrier CI (Mitochondrial) Complex I CC22 Chemokine (C-C motif) ligand 22 CD44v6 CD44 splicing variant 6 CDK4 Cyclin-dependent kinase 4 CDKN2A p16INK4A inhibitor of CDK4 cMAP Connectivity Map CNS Central nervous system COT Serine/threonine kinase Cot CRAF RAF proto-oncogene serine/threonine-protein kinase CT Computed tomography CTLA4 Cytotoxic T-lymphocyte-associated protein 4 CXCR4 C-X-C chemokine receptor type 4 2 Da Dalton (unit) DNA Deoxyribonucleic acid DWI Diffusion weighted imaging ECM Extracranial metastases EDNRB Endothelin receptor B EFSA European Foods Safety Authority EGFR Epidermal growth factor receptor ER Estrogen receptor ERBB2 Receptor tyrosine-protein kinase erbB-2 ERK Extracellular signal-regulated kinase ET3 Endothelin-3
    [Show full text]
  • Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
    Author Manuscript Published OnlineFirst on November 21, 2016; DOI: 10.1158/0008-5472.CAN-16-1901 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Systematic drug screening identifies tractable targeted combination therapies in triple-negative breast cancer Vikram B Wali1,3, Casey G Langdon2, Matthew A Held2, James T Platt1, Gauri A Patwardhan1, Anton Safonov1, Bilge Aktas1, Lajos Pusztai1,3, David F Stern2,3,Christos Hatzis1,3 1 Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA 2 Department of Pathology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA 3 Yale Cancer Center, New Haven Connecticut, USA Corresponding authors: Christos Hatzis, Ph.D. or Vikram B Wali, Ph.D. Section of Medical Oncology Yale School of Medicine Yale University 333 Cedar Street PO Box 208032 New Haven, CT 06520 [email protected] [email protected] Running Title: Novel Combination Therapies in Triple Negative Breast Cancer CONFLICTS OF INTEREST Authors have no conflict of interest to disclose. 1 Downloaded from cancerres.aacrjournals.org on October 6, 2021. © 2016 American Association for Cancer Research. Author Manuscript Published OnlineFirst on November 21, 2016; DOI: 10.1158/0008-5472.CAN-16-1901 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. ABSTRACT Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation.
    [Show full text]
  • The Effects of Targeted Deletion of the Aromatase Enzyme on Prostatic Contractile Responses to Noradrenaline in Mice
    495 The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice Katherine T Gray, Jennifer L Short, Evan R Simpson1 and Sabatino Ventura Prostate Research Co-operative, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia 1Prince Henry’s Institute of Medical Research, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia (Correspondence should be addressed to S Ventura; Email: [email protected]) Abstract This investigation aimed to see whether a change in the concentration-dependent contractions. Prazosin (0.3 mM) oestrogen to androgen ratio alters prostate contractility. Isolated attenuated the responses induced by noradrenaline and EFS in organ bath studies using prostates from aromatase knockout all mice (P%0.019, nZ5–7), while cocaine (10 mM) attenuated (ArKO) mice which were homozygous (ArKOK/K)and the responses evoked by tyramine (P!0.001, nZ6). There were heterozygous (ArKOC/K) for the disrupted aromatase cyp19 no genotype differences in EFS- and noradrenaline-induced gene and wild-type littermates (ArKOC/C) were conducted. responses (PR0.506, nZ10–13). Prostates from ArKOK/K The distribution of noradrenergic nerves was visualized using and ArKOC/K mice were more sensitive to tyramine than the sucrose–potassium phosphate–glyoxylic acid method. prostates from ArKOC/C mice (P!0.001, nZ11–13). Dense ArKOK/K mice had increased prostate weights compared adrenergic innervation of the prostate was similar in all mice. with ArKOC/C mice. Frequency–response curves to electrical These results suggest that although the absence of aromatase field stimulation (EFS; 0.5 ms pulse duration, 60 V,0.1–20 Hz) increases prostatic growth, this translates only to a subtle and yielded frequency-dependent contractions, while noradrenaline selective increase in contractility in mature mice.
    [Show full text]
  • Proteomics and Drug Repurposing in CLL Towards Precision Medicine
    cancers Review Proteomics and Drug Repurposing in CLL towards Precision Medicine Dimitra Mavridou 1,2,3, Konstantina Psatha 1,2,3,4,* and Michalis Aivaliotis 1,2,3,4,* 1 Laboratory of Biochemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; [email protected] 2 Functional Proteomics and Systems Biology (FunPATh)—Center for Interdisciplinary Research and Innovation (CIRI-AUTH), GR-57001 Thessaloniki, Greece 3 Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece 4 Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, GR-70013 Heraklion, Greece * Correspondence: [email protected] (K.P.); [email protected] (M.A.) Simple Summary: Despite continued efforts, the current status of knowledge in CLL molecular pathobiology, diagnosis, prognosis and treatment remains elusive and imprecise. Proteomics ap- proaches combined with advanced bioinformatics and drug repurposing promise to shed light on the complex proteome heterogeneity of CLL patients and mitigate, improve, or even eliminate the knowledge stagnation. In relation to this concept, this review presents a brief overview of all the available proteomics and drug repurposing studies in CLL and suggests the way such studies can be exploited to find effective therapeutic options combined with drug repurposing strategies to adopt and accost a more “precision medicine” spectrum. Citation: Mavridou, D.; Psatha, K.; Abstract: CLL is a hematological malignancy considered as the most frequent lymphoproliferative Aivaliotis, M. Proteomics and Drug disease in the western world. It is characterized by high molecular heterogeneity and despite the Repurposing in CLL towards available therapeutic options, there are many patient subgroups showing the insufficient effectiveness Precision Medicine.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9.421,180 B2 Zielinski Et Al
    USOO9421 180B2 (12) United States Patent (10) Patent No.: US 9.421,180 B2 Zielinski et al. (45) Date of Patent: Aug. 23, 2016 (54) ANTIOXIDANT COMPOSITIONS FOR 6,203,817 B1 3/2001 Cormier et al. .............. 424/464 TREATMENT OF INFLAMMATION OR 6,323,232 B1 1 1/2001 Keet al. ............ ... 514,408 6,521,668 B2 2/2003 Anderson et al. ..... 514f679 OXIDATIVE DAMAGE 6,572,882 B1 6/2003 Vercauteren et al. ........ 424/451 6,805,873 B2 10/2004 Gaudout et al. ....... ... 424/401 (71) Applicant: Perio Sciences, LLC, Dallas, TX (US) 7,041,322 B2 5/2006 Gaudout et al. .............. 424/765 7,179,841 B2 2/2007 Zielinski et al. .. ... 514,474 (72) Inventors: Jan Zielinski, Vista, CA (US); Thomas 2003/0069302 A1 4/2003 Zielinski ........ ... 514,452 Russell Moon, Dallas, TX (US); 2004/0037860 A1 2/2004 Maillon ...... ... 424/401 Edward P. Allen, Dallas, TX (US) 2004/0091589 A1 5, 2004 Roy et al. ... 426,265 s s 2004/0224004 A1 1 1/2004 Zielinski ..... ... 424/442 2005/0032882 A1 2/2005 Chen ............................. 514,456 (73) Assignee: Perio Sciences, LLC, Dallas, TX (US) 2005, 0137205 A1 6, 2005 Van Breen ..... 514,252.12 2005. O154054 A1 7/2005 Zielinski et al. ............. 514,474 (*) Notice: Subject to any disclaimer, the term of this 2005/0271692 Al 12/2005 Gervasio-Nugent patent is extended or adjusted under 35 et al. ............................. 424/401 2006/0173065 A1 8/2006 BeZwada ...................... 514,419 U.S.C. 154(b) by 19 days. 2006/O193790 A1 8/2006 Doyle et al.
    [Show full text]
  • Phenotype Microarrays Panels PM-M1 to PM-M14
    Phenotype MicroArrays™ Panels PM-M1 to PM-M14 for Phenotypic Characterization of Mammalian Cells Assays: Energy Metabolism Pathways Ion and Hormone Effects on Cells Sensitivity to Anti-Cancer Agents and for Optimizing Culture Conditions for Mammalian Cells PRODUCT DESCRIPTIONS AND INSTRUCTIONS FOR USE PM-M1 Cat. #13101 PM-M2 Cat. #13102 PM-M3 Cat. #13103 PM-M4 Cat. #13104 PM-M5 Cat. #13105 PM-M6 Cat. #13106 PM-M7 Cat. #13107 PM-M8 Cat. #13108 PM-M11 Cat. #13111 PM-M12 Cat. #13112 PM-M13 Cat. #13113 PM-M14 Cat. #13114 © 2016 Biolog, Inc. All rights reserved Printed in the United States of America 00P 134 Rev F February 2020 - 1 - CONTENTS I. Introduction ...................................................................................................... 2 a. Overview ................................................................................................... 2 b. Background ............................................................................................... 2 c. Uses ........................................................................................................... 2 d. Advantages ................................................................................................ 3 II. Product Description, PM-M1 to M4 ................................................................ 3 III. Protocols, PM-M1 to M4 ................................................................................. 7 a. Materials Required .................................................................................... 7 b. Determination
    [Show full text]
  • New Contributions in Undergraduate Research
    PSU McNair Scholars Online Journal Volume 11 Issue 1 Without Borders: Original Contributions Article 6 in Undergraduate Research 2017 Wings Outstretched: New Contributions in Undergraduate Research Follow this and additional works at: https://pdxscholar.library.pdx.edu/mcnair Let us know how access to this document benefits ou.y Recommended Citation (2017) "Wings Outstretched: New Contributions in Undergraduate Research," PSU McNair Scholars Online Journal: Vol. 11: Iss. 1, Article 6. https://doi.org/10.15760/mcnair.2017.01 This open access Full Issue is distributed under the terms of the Creative Commons Attribution-NonCommercial- ShareAlike 4.0 International License (CC BY-NC-SA 4.0). All documents in PDXScholar should meet accessibility standards. If we can make this document more accessible to you, contact our team. Portland State University McNair Research Journal 2017 Without Borders: Original Contributions in Undergraduate Research 2017 Ronald E. McNair Scholars Journal Portland State University 1 About the Program The Portland State University (PSU) Ronald E. McNair Scholars Program at Portland State University works with motivated and talented undergraduates who want to pursue PhDs. It introduces juniors and seniors who are first-generation and low income, and/or members of under-represented groups to academic research and to effective strategies for getting into and graduating from PhD programs. The McNair Scholars Program has academic-year activities and a full-time summer research internship. Scholars take academic and skills-building seminars and workshops during the year, and each scholar works closely with a faculty mentor on original research in the summer. Scholars present their research findings at the McNair Summer Symposium and at other conferences, and are encouraged to publish their papers in the McNair Journal and other scholarly publications.
    [Show full text]
  • Part I Biopharmaceuticals
    1 Part I Biopharmaceuticals Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 3 1 Analogs and Antagonists of Male Sex Hormones Robert W. Brueggemeier The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus, Ohio 43210, USA 1Introduction6 2 Historical 6 3 Endogenous Male Sex Hormones 7 3.1 Occurrence and Physiological Roles 7 3.2 Biosynthesis 8 3.3 Absorption and Distribution 12 3.4 Metabolism 13 3.4.1 Reductive Metabolism 14 3.4.2 Oxidative Metabolism 17 3.5 Mechanism of Action 19 4 Synthetic Androgens 24 4.1 Current Drugs on the Market 24 4.2 Therapeutic Uses and Bioassays 25 4.3 Structure–Activity Relationships for Steroidal Androgens 26 4.3.1 Early Modifications 26 4.3.2 Methylated Derivatives 26 4.3.3 Ester Derivatives 27 4.3.4 Halo Derivatives 27 4.3.5 Other Androgen Derivatives 28 4.3.6 Summary of Structure–Activity Relationships of Steroidal Androgens 28 4.4 Nonsteroidal Androgens, Selective Androgen Receptor Modulators (SARMs) 30 4.5 Absorption, Distribution, and Metabolism 31 4.6 Toxicities 32 Translational Medicine: Molecular Pharmacology and Drug Discovery First Edition. Edited by Robert A. Meyers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA. 4 Analogs and Antagonists of Male Sex Hormones 5 Anabolic Agents 32 5.1 Current Drugs on the Market 32 5.2 Therapeutic Uses and Bioassays
    [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]
  • Chronic Lymphocytic Leukemia
    Amsterdam, the Netherlands, June 14 – 17, 2012 Chronic lymphocytic leukemia - Clinical 1 assumed efficacy especially in high-risk situations (early relapse, unfavourable prognostic markers), was used in 202 patients. The overall survival in the CHOP-collective was significantly shorter than in the comparative group (p<0.0001) although median observation time was not significantly differ - 0144 ent. However, this observation might reflect a bias in the selection of high risk patients for this relapse treatment. No influence on survival was INFLUENCE OF DIFFERENT TREATMENT REGIMENS ON SURVIVAL IN observed in patients receiving a mitoxantrone-containing regimen at any PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA - A META-ANALY - time during the treatment course. Summary and Conclusions. This meta- SIS OF THE GERMAN CLL STUDY GROUP (GCLLSG) analysis shows that the advances in the development of strategies for first- S Isfort 1, P Cramer 2, J Bahlo 2, R Busch 3, K Fischer 2, AM Fink 2, V Goede 2, T line therapies result in prolongation of treatment-free and overall survival Elter 2, M Bergmann 4, M Stauch 5, S Stilgenbauer 4, CM Wendtner 6, M Hallek 2, for patients with CLL and need of treatment. Chemoimmunotherapies pro - B Eichhorst 2 long the survival independently of the time point of chemoimmunotherapy 1Department of Medicine IV, University Hospital Aachen, Aachen, Germany administration (for first-line therapy or relapse). 2Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany 3 Institute for Medical Statistic and Epidemiology, Technical University Munich, 0145 Munich, Germany 4 Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany A SINGLE-ARM MULTI-CENTER TRIAL OF BENDAMUSTINE GIVEN 5 Private practice and day time clinic for Hematology and Oncology, Kronach, WITH OFATUMUMAB (BENDOFA) IN PATIENTS WITH REFRACTORY OR Kronach, Germany RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA.
    [Show full text]
  • Natural Chalcones in Chinese Materia Medica: Licorice
    Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 3821248, 14 pages https://doi.org/10.1155/2020/3821248 Review Article Natural Chalcones in Chinese Materia Medica: Licorice Danni Wang ,1 Jing Liang,2 Jing Zhang,1 Yuefei Wang ,1 and Xin Chai 1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 2School of Foreign Language, Chengdu University of Traditional Chinese Medicine, Sichuan 611137, China Correspondence should be addressed to Xin Chai; [email protected] Received 28 August 2019; Accepted 7 February 2020; Published 15 March 2020 Academic Editor: Veronique Seidel Copyright © 2020 Danni Wang et al. -is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Licorice is an important Chinese materia medica frequently used in clinical practice, which contains more than 20 triterpenoids and 300 flavonoids. Chalcone, one of the major classes of flavonoid, has a variety of biological activities and is widely distributed in nature. To date, about 42 chalcones have been isolated and identified from licorice. -ese chalcones play a pivotal role when licorice exerts its pharmacological effects. According to the research reports, these compounds have a wide range of biological activities, containing anticancer, anti-inflammatory, antimicrobial, antioxidative, antiviral, antidiabetic, antidepressive, hep- atoprotective activities, and so on. -is review aims to summarize structures and biological activities of chalcones from licorice. We hope that this work can provide a theoretical basis for the further studies of chalcones from licorice.
    [Show full text]