Aspects of the Usage of Antineoplastic and 1Mmunomodulating Agents in a Section of the Private Health Care Sector
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(201 1.01) A61k 31/713
( (51) International Patent Classification: S McAllister Ave., Tempe, Arizona 85281 (US). ZHANG, C12N 15/11 7 (20 10.01) B82Y 5/00 (201 1.01) Fei; 5460 S Scott PI, Chandler, Arizona 85249 (US). A61K 31/713 (2006.01) C12N 15/115 (2010.01) (74) Agent: NORTON, Vicki G.; DUANE MORRIS LLP, 750 A61K 39/39 (2006.01) B Street, Suite 2900, San Diego, California 92101-4681 (21) International Application Number: (US). PCT/U S201 9/013 118 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of national protection av ailable) . AE, AG, AL, AM, 10 January 2019 (10.01.2019) 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, 62/615,806 10 January 2018 (10.01.2018) US OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (71) Applicant: ARIZONA BOARD OF REGENTS ON BE¬ SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, HALF OF ARIZONA STATE UNIVERSITY [US/US]; TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 1475 North Scottsdale Road, SkySong - Suite 200, Scotts¬ (84) Designated States (unless otherwise indicated, for every dale, Arizona 85257-3538 (US). -
Thymic Peptides and Preparations: an Update
¡ Archivum Immunologiae et Therapiae Experimentalis, 1999, 47¢ , 77–82 £ PL ISSN 0004-069X Review Thymic Peptides and Preparations: an Update ¤ O. J. Cordero et al.: Thymic Peptides ¦ ¨ § OSCAR J. CORDERO, A¥ LICIA PIÑEIRO and MONTSERRAT NOGUEIRA Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain Abstract. The possibilities of thymic peptides in human therapy are still being described. Here, we focus on their © general characteristics and on recent advances in this area. Key words: thymus; thymic peptides; preclinical investigation; therapeutic use; clinical trials. Thymic peptides, as well as a variety of other purified from porcine and human serum and from calf modulators (IL-1, IL-3, IL-6, GM-CSF) and cell-cell thymus, and named “facteur thymique serique”11. interactions, regulate the process known as thymic se- According to the classical criteria, TH is the unique lection by which pro-thymocytes become mature and peptide that can be recognized as a hormone. Its secre- functional T cells. tion by a subpopulation of thymic epithelial cells (TEC) Several polypeptides have been extracted, mainly is controlled by a pleiotropic mechanism involving its from young calves, and some of them have been suc- own levels and those of prolactine (PRL), growth hor- cessfully isolated and prepared synthetically (Fig. 1). mone (GH) through insulin growth factor 1 (IGF-1) se- The precise role of much of these factors purported to cretion, adrenocorticotropin (ACTH), thyroxin (T4), β- have intrathymic effects is still unknown, although endorphin and β-leukencephalin and IL-1α and β8. many of these compounds exhibit immunobiological Furthermore, reciprocal regulatory actions on the activity. -
By Exemestane, a Novel Irreversible Aromatase Inhibitor, in Postmenopausal Breast Cancer Patients1
Vol. 4, 2089-2093, September 1998 Clinical Cancer Research 2089 In Vivo Inhibition of Aromatization by Exemestane, a Novel Irreversible Aromatase Inhibitor, in Postmenopausal Breast Cancer Patients1 Jfirgen Geisler, Nick King, Gun Anker, ation aromatase inhibitor AG3 has been used for breast cancer Giorgio Ornati, Enrico Di Salle, treatment for more than two decades (1). Because of substantial side effects associated with AG treatment, several new aro- Per Eystein L#{248}nning,2 and Mitch Dowsett matase inhibitors have been introduced in clinical trials. Department of Oncology, Haukeland University Hospital, N-502l Aromatase inhibitors can be divided into two major classes Bergen, Norway [J. G., G. A., P. E. L.]; Academic Department of Biochemistry, Royal Marsden Hospital, London, SW3 6JJ, United of compounds, steroidal and nonsteroidal drugs. Nonsteroidal Kingdom [N. K., M. D.]; and Department of Experimental aromatase inhibitors include AG and the imidazole/triazole Endocrinology, Pharmacia and Upjohn, 20014 Nerviano, Italy [G. 0., compounds. With the exception of testololactone, a testosterone E. D. S.] derivative (2), steroidal aromatase inhibitors are all derivatives of A, the natural substrate for the aromatase enzyme (3). The second generation steroidal aromatase inhibitor, 4- ABSTRACT hydroxyandrostenedione (4-OHA, formestane), was found to The effect of exemestane (6-methylenandrosta-1,4- inhibit peripheral aromatization by -85% when administered diene-3,17-dione) 25 mg p.o. once daily on in vivo aromati- by the i.m. route at a dosage of 250 mg every 2 weeks as zation was studied in 10 postmenopausal women with ad- recommended (4) but only by 50-70% (5) when administered vanced breast cancer. -
Thymopentin and Splenopentin As Immunomodulators Current Stutus
Immunologic Research 1998;17/3:345-368 Thymopentin and Splenopentin as Immunomodulators Current Stutus 1Department of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India. 2Division of Biopolymers, Central Drug Research Institute, Lucknow, India. 3Department of Microbiology, RML Awadh University, Faizabad, India. Abstract Key Words Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Immunomodulation Arg-Lys-Asp-Val-Tyr) are synthetic immunomodulating peptides Splenin corresponding to the region 32-34 of a splenic product called splenin Splenopentin (SP) and the thymic hormone thymopoietin (TP), respectively. TP Thymopoietin was originally isolated as a 5-kDa (49-amino acids) protein from Thymopentin bovine thymus while studying effects of the thymic extracts on neuro- muscular transmission and was subsequently observed to affect T cell differentiation and function. TP I and II are two closely related polypeptides isolated from bovine thymus. A radioimmunoassay for TP revealed a crossreaction with a product found in spleen and lymph node. This product, named splenin, differs from TP only in position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5), reproduce the biological activities of TP and SP, respectively. It is now evident that various forms of TPs were created by proteolytic cleavage of larger proteins during isolation, cDNA clones have been isolated for three alternatively spliced mRNAs that encodes three distinct human T cell TPs. The immunomodulatory properties of TP, SP, TP-5, SP-5 and some of their synthetic analogs reported in the literature have been briefly reviewed. -
Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors
View metadata, citation and similar papers at core.ac.uk brought to you by CORE J. Med. Chem. 2009, 52, 143–150 143 provided by Estudo Geral Fast Three Dimensional Pharmacophore Virtual Screening of New Potent Non-Steroid Aromatase Inhibitors Marco A. C. Neves,† Teresa C. P. Dinis,‡ Giorgio Colombo,*,§ and M. Luisa Sa´ e Melo*,† Centro de Estudos Farmaceˆuticos, Laborato´rio de Quı´mica Farmaceˆutica, Faculdade de Farma´cia, UniVersidade de Coimbra, 3000-295, Coimbra, Portugal, Centro de Neurocieˆncias, Laborato´rio de Bioquı´mica, Faculdade de Farma´cia, UniVersidade de Coimbra, 3000-295, Coimbra, Portugal, and Istituto di Chimica del Riconoscimento Molecolare, CNR, 20131, Milano, Italy ReceiVed July 28, 2008 Suppression of estrogen biosynthesis by aromatase inhibition is an effective approach for the treatment of hormone sensitive breast cancer. Third generation non-steroid aromatase inhibitors have shown important benefits in recent clinical trials with postmenopausal women. In this study we have developed a new ligand- based strategy combining important pharmacophoric and structural features according to the postulated aromatase binding mode, useful for the virtual screening of new potent non-steroid inhibitors. A small subset of promising drug candidates was identified from the large NCI database, and their antiaromatase activity was assessed on an in vitro biochemical assay with aromatase extracted from human term placenta. New potent aromatase inhibitors were discovered to be active in the low nanomolar range, and a common binding mode was proposed. These results confirm the potential of our methodology for a fast in silico high-throughput screening of potent non-steroid aromatase inhibitors. Introduction built and proved to be valuable in understanding the binding 14-16 Aromatase, a member of the cytochrome P450 superfamily determinants of several classes of inhibitors. -
(12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin Et Al
US 201201.15729A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin et al. (43) Pub. Date: May 10, 2012 (54) PROCESS FOR FORMING FILMS, FIBERS, Publication Classification AND BEADS FROM CHITNOUS BOMASS (51) Int. Cl (75) Inventors: Ying Qin, Tuscaloosa, AL (US); AOIN 25/00 (2006.01) Robin D. Rogers, Tuscaloosa, AL A6II 47/36 (2006.01) AL(US); (US) Daniel T. Daly, Tuscaloosa, tish 9.8 (2006.01)C (52) U.S. Cl. ............ 504/358:536/20: 514/777; 426/658 (73) Assignee: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF 57 ABSTRACT ALABAMA, Tuscaloosa, AL (US) (57) Disclosed is a process for forming films, fibers, and beads (21) Appl. No.: 13/375,245 comprising a chitinous mass, for example, chitin, chitosan obtained from one or more biomasses. The disclosed process (22) PCT Filed: Jun. 1, 2010 can be used to prepare films, fibers, and beads comprising only polymers, i.e., chitin, obtained from a suitable biomass, (86). PCT No.: PCT/US 10/36904 or the films, fibers, and beads can comprise a mixture of polymers obtained from a suitable biomass and a naturally S3712). (4) (c)(1), Date: Jan. 26, 2012 occurring and/or synthetic polymer. Disclosed herein are the (2), (4) Date: an. AO. films, fibers, and beads obtained from the disclosed process. O O This Abstract is presented solely to aid in searching the sub Related U.S. Application Data ject matter disclosed herein and is not intended to define, (60)60) Provisional applicationpp No. 61/182,833,sy- - - s filed on Jun. -
Stems for Nonproprietary Drug Names
USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol -
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine -
(12) United States Patent (10) Patent No.: US 8,580,267 B2 Pedretti Et Al
US008580267B2 (12) United States Patent (10) Patent No.: US 8,580,267 B2 Pedretti et al. (45) Date of Patent: Nov. 12, 2013 (54) IMMUNOCYTOKINES FORTUMOUR (56) References Cited THERAPY WITH CHEMOTHERAPEUTIC AGENTS FOREIGN PATENT DOCUMENTS (75) Inventors: Marta Pedretti, Zurich (CH): Dario WO O2/O59264 8, 2002 WO O3,O93478 11, 2003 Neri, Buchs (CH) WO 2004/OO2528 1, 2004 WO 2006/026020 3, 2006 (73) Assignee: Philogen S.p.A., Siena (IT) WO 2006/050834 5, 2006 WO 2007/128563 11, 2007 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. Paul, William, Fundamental Immunology, 3rd Edition, Raven Press, New York, 1993, pp. 292-295.* (21) Appl. No.: 13/139,655 Vajdos et al., Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning 1-1. mutagenesis. J. Mol. Biol. 320:415-428, 2002.* (22) PCT Filed: Dec. 14, 2009 Bartolomei, M., et al. “Combined treatment of glioblastomapatients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and (86). PCT No.: PCT/EP2009/008920 temozolomide.” QJNuclMed Mol Imaging. Sep. 2004:48(3):220-8. S371 (c)(1) Marlind, J., et al. "Antibody-mediated delivery of interleukin-2 to the (2), (4) Date. Jun. 14, 2011 Stroma of breast cancer strongly enhances the potency of chemo s 9 therapy” Clin Cancer Res. Oct. 15, 2008;14(20):6515-24. Brack, S.S., et al. “Tumor-targeting properties of novel antibodies (87) PCT Pub. No.: WO2010/078916 specific to the large isoform oftenascin-C.” Clin Cancer Res. -
Ep 2569287 B1
(19) TZZ _T (11) EP 2 569 287 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 413/04 (2006.01) C07D 239/46 (2006.01) 09.07.2014 Bulletin 2014/28 (86) International application number: (21) Application number: 11731562.2 PCT/US2011/036245 (22) Date of filing: 12.05.2011 (87) International publication number: WO 2011/143425 (17.11.2011 Gazette 2011/46) (54) COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE VERBINDUNGEN ALS HEMMER DER ATR-KINASE COMPOSÉS UTILISABLES EN TANT QU’INHIBITEURS DE LA KINASE ATR (84) Designated Contracting States: • VIRANI, Aniza, Nizarali AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Abingdon GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Oxfordshire OX144RY (GB) PL PT RO RS SE SI SK SM TR • REAPER, Philip, Michael Abingdon (30) Priority: 12.05.2010 US 333869 P Oxfordshire OX144RY (GB) (43) Date of publication of application: (74) Representative: Coles, Andrea Birgit et al 20.03.2013 Bulletin 2013/12 Kilburn & Strode LLP 20 Red Lion Street (73) Proprietor: Vertex Pharmaceuticals Inc. London WC1R 4PJ (GB) Boston, MA 02210 (US) (56) References cited: (72) Inventors: WO-A1-2010/054398 WO-A1-2010/071837 • CHARRIER, Jean-Damien Abingdon • C. A. HALL-JACKSON: "ATR is a caffeine- Oxfordshire OX144RY (GB) sensitive, DNA-activated protein kinase with a • DURRANT, Steven, John substrate specificity distinct from DNA-PK", Abingdon ONCOGENE, vol. 18, 1999, pages 6707-6713, Oxfordshire OX144RY (GB) XP002665425, cited in the application • KNEGTEL, Ronald, Marcellus Alphonsus Abingdon Oxfordshire OX144RY (GB) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. -
Preliminary Data from Ongoing Adjuvant Aromatase Inhibitor Trials I
Vol. 7, 4397s-4401s, December 2001 (Suppl.) Clinical Cancer Research 4397s Preliminary Data from Ongoing Adjuvant Aromatase Inhibitor Trials I Paul E. Goss z Introduction Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada The growth of hormone receptor-positive breast cancer can be altered clinically by several classes of agents that antagonize the effects of estrogen (1). The SERMs, 3 exemplified by tamox- Abstract ifen, constitute one such class of drugs. Pure antiestrogens such With recent results showing letrozole and anastrozole as fulvestrant (Faslodex) also exert a potent antiestrogenic effect to be superior to tamoxifen as initial therapy for advanced and show efficacy in tamoxifen-resistant cell lines in preclinical disease, the aromatase inhibitors are poised to establish their models. Thus, unlike tamoxifen, which exerts both an agonist place in the adjuvant therapy of postmenopausal receptor- and an antagonist effect, fulvestrant is a pure antagonist and acts positive breast cancer. A review of the rationale, design, and by down-regulating ER content (2). preliminary results of the ongoing adjuvant trials that in- Aromatase (estrogen synthetase) inhibitors antagonize the clude aromatase inhibitors will be presented, along with the action of estrogen by reducing its levels both in the circulation ongoing or planned substudies. Two strategies employing and in normal and malignant breast tissue (3). They were ini- aromatase inhibitors after tamoxifen are being evaluated. tially tested in postmenopausal women with breast cancer pro- gression after tamoxifen treatment. A superior outcome with The MA.17 international intergroup trial is randomizing these drugs compared to either megestrol acetate or aminoglu- postmenopausal patients who are disease-free after 5 years tethimide resulted in their becoming the established second-line of adjuvant tamoxifen to an additional 5 years of ietrozole or treatment for ER-positive metastatic breast cancer (4-13). -
Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R
Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R. SIMPSON* AND MITCH DOWSETT *Prince Henry’s Institute of Medical Research, Monash Medical Centre, Clayton, Victoria 3168, Australia; †Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, United Kingdom ABSTRACT Endocrine adjuvant therapy for breast cancer in recent years has focussed primarily on the use of tamoxifen to inhibit the action of estrogen in the breast. The use of aromatase inhibitors has found much less favor due to poor efficacy and unsustainable side effects. Now, however, the situation is changing rapidly with the introduction of the so-called phase III inhibitors, which display high affinity and specificity towards aromatase. These compounds have been tested in a number of clinical settings and, almost without exception, are proving to be more effective than tamoxifen. They are being approved as first-line therapy for elderly women with advanced disease. In the future, they may well be used not only to treat young, postmenopausal women with early-onset disease but also in the chemoprevention setting. However, since these compounds inhibit the catalytic activity of aromatase, in principle, they will inhibit estrogen biosynthesis in every tissue location of aromatase, leading to fears of bone loss and possibly loss of cognitive function in these younger women. The concept of tissue-specific inhibition of aromatase expression is made possible by the fact that, in postmenopausal women when the ovaries cease to produce estrogen, estrogen functions primarily as a local paracrine and intracrine factor. Furthermore, due to the unique organization of tissue-specific promoters, regulation in each tissue site of expression is controlled by a unique set of regulatory factors.