Translating Jaks to Jakinibs Massimo Gadina, Danielle A
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Stanford Chem-H Presentation (PDF)
KiNativ® In situ kinase profiling Stanford University ChEM-H confidential @KiNativPlatform Principle of the KiNativ platform • ATP (or ADP) acyl phosphate binds to, and covalently modifies Lysine residues in the active site • Thus, ATP acyl phosphate with a desthiobiotin tag can be used capture and quantitate kinases in a complex lysate Acyl phosphate Desthiobiotin tag ATP 2 ATP acyl phosphate probe covalently modifies kinase in the active site Lysine 2 Lysine 1 3 ATP acyl phosphate probe covalently modifies kinase in the active site Lysine 2 Lysine 1 4 Samples trypsinized, probe-labeled peptides captured with streptavidin, and analyzed by targeted LC-MS2 Identification Quantitation Explicit determination of peptide Integration of signal from MS2 sequence and probe modification site fragment ions from MS2 spectrum 5 Comprehensive Coverage of Protein and Lipid Kinases Protein kinases Atypical kinases Green: Kinases detected on KiNativ Red: Kinases not detected on KiNativ ~80% of known protein and atypical kinases identified on the platform http://www.kinativ.com/coverage/protein-lipid.html 6 Profiling compound(s) on the KiNativ platform Control sample – add probe Sample: Lysate derived from any cell line or tissue from ANY species Treated sample – add inhibitor followed by probe Inhibited kinase Green: Kinases Blue: Probe Gray: Non-kinases Red: Inhibitor 7 Profiling compound(s) on the KiNativ platform Control sample – add probe MS signalMS Sample: Lysate derived from any cell line or tissue from ANY species Treated sample – add inhibitor -
CVMP Assessment Report for APOQUEL (EMEA/V/C/002688/0000) International Non-Proprietary Name: Oclacitinib Maleate
18 July 2013 EMA/481054/2013 Veterinary Medicines and Product Data Management Committee for Medicinal Products for Veterinary Use CVMP assessment report for APOQUEL (EMEA/V/C/002688/0000) International non-proprietary name: oclacitinib maleate Assessment report as adopted by the CVMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8447 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged. Introduction The applicant Pfizer Animal Health S.A. submitted on 26 July 2012 an application for marketing authorisation to the European Medicines Agency (The Agency) for APOQUEL, through the centralised procedure falling within Article 3(2)(a) of Regulation (EC) No 726/2004 (new active substance). During the procedure the applicant changed to Zoetis Belgium S.A. The eligibility to the centralised procedure was confirmed by the CVMP on 12 January 2012 falling under Article 3(2)(a) of Regulation (EC) No 726/2004 as APOQUEL contains a new active substance which was not authorised in the Community on the date of entry into force of the Regulation. APOQUEL film-coated tablets contain oclacitinib (as oclacitinib maleate) as the active substance. There are three different strengths of the (film-coated) tablets, containing 3.6 mg, 5.4 mg and 16 mg oclacitinib (as the maleate salt), and each is contained in blister packs (polychlorotrifluoroethylene (PCTFE)/polyvinylchloride (PVC)/aluminium) which are supplied in outer cartons containing 20 or 100 tablets. -
Stem Cell Factor Is Selectively Secreted by Arterial Endothelial Cells in Bone Marrow
ARTICLE DOI: 10.1038/s41467-018-04726-3 OPEN Stem cell factor is selectively secreted by arterial endothelial cells in bone marrow Chunliang Xu1,2, Xin Gao1,2, Qiaozhi Wei1,2, Fumio Nakahara 1,2, Samuel E. Zimmerman3,4, Jessica Mar3,4 & Paul S. Frenette 1,2,5 Endothelial cells (ECs) contribute to haematopoietic stem cell (HSC) maintenance in bone marrow, but the differential contributions of EC subtypes remain unknown, owing to the lack 1234567890():,; of methods to separate with high purity arterial endothelial cells (AECs) from sinusoidal endothelial cells (SECs). Here we show that the combination of podoplanin (PDPN) and Sca-1 expression distinguishes AECs (CD45− Ter119− Sca-1bright PDPN−) from SECs (CD45− Ter119− Sca-1dim PDPN+). PDPN can be substituted for antibodies against the adhesion molecules ICAM1 or E-selectin. Unexpectedly, prospective isolation reveals that AECs secrete nearly all detectable EC-derived stem cell factors (SCF). Genetic deletion of Scf in AECs, but not SECs, significantly reduced functional HSCs. Lineage-tracing analyses suggest that AECs and SECs self-regenerate independently after severe genotoxic insults, indicating the per- sistence of, and recovery from, radio-resistant pre-specified EC precursors. AEC-derived SCF also promotes HSC recovery after myeloablation. These results thus uncover heterogeneity in the contribution of ECs in stem cell niches. 1 The Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY 10461, USA. 2 Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA. 3 Department of Systems and Computational Biology, Albert Einstein College of Medicine, New York, NY 10461, USA. -
European Iron Club 7
EUROPEAN IRON CLUB 7 - 10 MEETING IN April INNSBRUCK 2016 Programme Kein Eisen unter der Oberfläche Novartis Pharma GmbH Stella-Klein-Loew-Weg 17 | 1020 Wien www.novartispharma.at | +43 1 866 57-0 Erstellungsdatum 02/2016 | AT1602436490 CONTENTS Welcome 6 Committees 7 Masterclass in Iron Therapies 8 Thursday, 7 April 2016 European Iron Club Annual Meeting 10 Friday, 8 April 2016 European Iron Club Annual Meeting 20 Saturday, 9 April 2016 Scientific Programme 31 Kein Eisen Sunday, 10 April 2016 Innsbruck city map 34 unter der General Information 35 Exhibitors & Sponsors 40 Oberfläche Drug labels 41 Notes 42 Novartis Pharma GmbH 3 Stella-Klein-Loew-Weg 17 | 1020 Wien www.novartispharma.at | +43 1 866 57-0 Erstellungsdatum 02/2016 | AT1602436490 CONGRESS INFORMATION DATES CONGRESS ORGANISER Masterclass in Iron Therapies PCO TYROL CONGRESS Thursday, 7 April, 2016 MMag. Ina Kähler Mechthild Walter European Iron Club Annual Rennweg 3 Meeting 6020 Innsbruck Friday, 8 April – Saturday, 9 April, Austria 2016 T: +43 (0) 512 575600 F: +43 (0) 512 575607 Non HFE Hemochromatosis E: [email protected] Registry Meeting I: www.pco-tyrolcongress.at Sunday, 10 April, 2016 Meeting of Patient Organisations Sunday, 10 April, 2016 EXHIBITION MANAGEMENT AND SPONSORING VENUE (THU - SAT) S12! STUDIO12 GMBH CONGRESS INNSBRUCK Ralph Kerschbaumer Rennweg 3 Kaiser Josef Straße 9 6020 Innsbruck 6020 Innsbruck Austria Austria www.cmi.at T: +43 (0) 512 890438 F: +43 (0) 512 890438 15 E: [email protected] I: www.studio12.co.at VENUE (SUN) AUSTRIA TREND HOTEL Rennweg 12a -
Survival Pathways That Regulate Macrophage Tec and Btk in M-CSF
Essential Roles for the Tec Family Kinases Tec and Btk in M-CSF Receptor Signaling Pathways That Regulate Macrophage Survival This information is current as of September 26, 2021. Martin Melcher, Bernd Unger, Uwe Schmidt, Iiro A. Rajantie, Kari Alitalo and Wilfried Ellmeier J Immunol 2008; 180:8048-8056; ; doi: 10.4049/jimmunol.180.12.8048 http://www.jimmunol.org/content/180/12/8048 Downloaded from References This article cites 36 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/180/12/8048.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 26, 2021 *average 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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Essential Roles for the Tec Family Kinases Tec and Btk in M-CSF Receptor Signaling Pathways That Regulate Macrophage Survival1 Martin Melcher,2* Bernd Unger,2† Uwe Schmidt,3* Iiro A. -
How I Treat Myelofibrosis
From www.bloodjournal.org by guest on October 7, 2014. For personal use only. Prepublished online September 16, 2014; doi:10.1182/blood-2014-07-575373 How I treat myelofibrosis Francisco Cervantes Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Advance online articles have been peer reviewed and accepted for publication but have not yet appeared in the paper journal (edited, typeset versions may be posted when available prior to final publication). Advance online articles are citable and establish publication priority; they are indexed by PubMed from initial publication. Citations to Advance online articles must include digital object identifier (DOIs) and date of initial publication. Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved. From www.bloodjournal.org by guest on October 7, 2014. For personal use only. Blood First Edition Paper, prepublished online September 16, 2014; DOI 10.1182/blood-2014-07-575373 How I treat myelofibrosis By Francisco Cervantes, MD, PhD, Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain Correspondence: Francisco Cervantes, MD, Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Phone: +34 932275428. -
Clinical Policy: Baricitinib (Olumiant) Reference Number: ERX.SPA.291 Effective Date: 07.24.18 Last Review Date: 11.18 Revision Log
Clinical Policy: Baricitinib (Olumiant) Reference Number: ERX.SPA.291 Effective Date: 07.24.18 Last Review Date: 11.18 Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Baricitinib (Olumiant®) is Janus kinase (JAK) inhibitor. FDA Approved Indication(s) Olumiant is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Limitation(s) of use: Use of Olumiant in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Envolve Pharmacy Solutions™ that Olumiant is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Rheumatoid Arthritis (must meet all): 1. Diagnosis of RA; 2. Prescribed by or in consultation with a rheumatologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a or b): a. Failure of a ≥ 3 consecutive month trial of methotrexate (MTX) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; b. If intolerance or contraindication to MTX (see Appendix D), failure of a ≥ 3 consecutive month trial of at least ONE conventional DMARD (e.g., sulfasalazine, leflunomide, hydroxychloroquine) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 5. -
WO 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT
(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 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT (51) International Patent Classification: (71) Applicant: JUNO THERAPEUTICS, INC. [US/US]; 400 A 61K 35/1 7 (20 15.0 1) A 61P 35/00 (2006 .0 1) Dexter Ave. N., Suite 1200, Seattle, WA 98109 (US). (21) International Application Number: (72) Inventor: ALBERTSON, Tina; 400 Dexter Ave. N., Suite PCT/US2018/035755 1200, Seattle, WA 98109 (US). (22) International Filing Date: (74) Agent: AHN, Sejin et al; Morrison & Foerster LLP, 1253 1 0 1 June 2018 (01 .06.2018) High Bluff Drive, Suite 100, San Diego, CA 92130-2040 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of national protection available): AE, AG, AL, AM, (30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/5 14,774 02 June 2017 (02.06.2017) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/5 15,530 05 June 2017 (05.06.2017) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/521,366 16 June 2017 (16.06.2017) u s HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/527,000 29 June 2017 (29.06.2017) u s KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 62/549,938 24 August 2017 (24.08.2017) u s MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/580,425 0 1 November 2017 (01 .11.2017) u s OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/593,871 0 1 December 2017 (01 .12.2017) u s SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/596,764 08 December 2017 (08.12.2017) u s TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Quality Report 2020/21 Royal Devon and Exeter NHS Foundation Trust
Quality Report 2020/21 Royal Devon and Exeter NHS Foundation Trust HOME . COMMUNITY- .1 HOSPITAL - WE WORK TOGETHER Quality Report 2020/21 CONTENTS Page Chief Executive’s Introduction ......................................................................................................................1 Progress on our 2020/21 Priorities: Governor Priorities ..............................................................................3 Progress on our 2020/21 Priorities: Trust Priorities .....................................................................................6 Improvements to Quality and Safety 2020/21 .............................................................................................7 Our Priorities for 2021/22: Governor Priorities ..........................................................................................15 Our Priorities for 2021/22: Trust Priorities .................................................................................................16 Duty of Candour ..........................................................................................................................................18 Learning from Deaths ..................................................................................................................................18 Seven Day Services ......................................................................................................................................21 NHS Staff Survey Results for indicators KR19 and KF27 ...........................................................................21 -
Redox-Mediated Regulation of the Tyrosine Kinase Zap70
Redox-mediated regulation of the tyrosine kinase Zap70 DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) genehmigt durch die Fakultät für Naturwissenschaften der Otto-von-Guericke-Universität von M.Sc. Christoph Thurm geb. am 27.06.1988 in Borna Gutachter: apl. Prof. Dr. Luca Simeoni PD Dr. rer. nat. Marcus Lettau eingereicht am: 02.02.2018 verteidigt am: 06.06.2018 Eigenständigkeitserklärung I. Eigenständigkeitserklärung Christoph Thurm Halberstädter Straße 29 39112 Magdeburg Hiermit erkläre ich, dass ich die von mir eingereichte Dissertation zu dem Thema Redox-mediated regulation of the tyrosine kinase Zap70 selbständig verfasst, nicht schon als Dissertation verwendet habe und die benutzten Hilfsmittel und Quellen vollständig angegeben wurden. Weiterhin erkläre ich, dass ich weder diese noch eine andere Arbeit zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) an anderen Einrichtungen eingereicht habe. Magdeburg, den 02.02.2018 ____________________________________ M.Sc. Christoph Thurm II ACKNOWLEDGEMENTS II. Acknowledgements Firstly, I would like to express my sincere gratitude to my supervisor Prof. Dr. Luca Simeoni. His extraordinary support during my PhD thesis together with his motivation and knowledge enabled me to pursue my dream. I could not have imagined having a better mentor. Furthermore, I would like to thank Prof. Dr. Burkhart Schraven for giving me the opportunity to work in his institute. His support, ideas, and the lively discussions promoted me to develop as a scientist. Special thanks go also to the whole AG Simeoni/Schraven - Ines, Camilla, Matthias, and Andreas - for the help with experiments, the discussions, and the fun we had. This helped to sustain also the longest days. -
Download Product Insert (PDF)
PRODUCT INFORMATION Pacritinib Item No. 16709 CAS Registry No.: 937272-79-2 Formal Name: 11-[2-(1-pyrrolidinyl)ethoxy]-14,19-dioxa- 5,7,27-triazatetracyclo[19.3.1.12,6.18,12] O heptacosa-1(25),2,4,6(27),8,10,12(26), 16E,21,23-decaene Synonym: SB1518 N N H MF: C28H32N4O3 FW: 472.6 N Purity: ≥98% O Stability: ≥2 years at -20°C Supplied as: A crystalline solid N O UV/Vis.: λmax: 285 nm Laboratory Procedures For long term storage, we suggest that pacritinib be stored as supplied at -20°C. It should be stable for at least two years. Pacritinib is supplied as a crystalline solid. A stock solution may be made by dissolving the pacritinib in the solvent of choice. Pacritinib is soluble in the organic solvent DMSO, which should be purged with an inert gas, at a concentration of approximately 0.5 mg/ml (slightly warmed). Pacritinib is sparingly soluble in aqueous solutions. To enhance aqueous solubility, dilute the organic solvent solution into aqueous buffers or isotonic saline. If performing biological experiments, ensure the residual amount of organic solvent is insignificant, since organic solvents may have physiological effects at low concentrations. We do not recommend storing the aqueous solution for more than one day. Description FMS-like tyrosine kinase 3 (FLT3) and Janus kinase 2 (JAK2) are tyrosine kinases that mediate cytokine signaling and are frequently mutated in cancers, particularly acute myeloid leukemia.1,2 Pacritinib is an 1 inhibitor of both FLT3 and JAK2 (IC50s = 22 and 23 nM, respectively). -
Heart Failure and Drug-Induced Lupus
Unusual toxicities with TNF inhibition: Heart failure and drug-induced lupus J.J. Cush John J. Cush, MD, Chief, Rheumatology ABSTRACT demyelinating disease, cytopenias, auto- and Clinical Immunology, Presbyterian Serious and unexpected adverse events, immune disorders, and heart failure. Hospital of Dallas, Clinical Professor of such as heart failure and drug-induced Other essays in this volume address the Internal Medicine, The University of Texas lupus, have been reported in patients subject of infection (10), demyelination Southwestern Medical School, Dallas, Texas, USA. receiving TNF inhibitor therapy. These (11), and lymphoma (12). This review events generally are easily recogniz- will focus on heart failure and lupus- Please address correspondence to: John J. Cush, MD, Presbyterian Hospital able, although they cannot be predicted like disease, which are rarely seen in of Dallas, 8200 Walnut Hill Lane, Dallas, nor avoided, other than by drug avoid- association with TNF inhibitor therapy Texax 75231-4496, USA. ance altogether. Many patients have and are currently without explanation. Clin Exp Rheumatol 2004; 22 (Suppl. 35): great benefit from anti-TNF therapies. S141-S147. Their intelligent use requires a firm Sources of data © Copyright CLINICAL AND EXPERIMENTAL understanding of these rare toxicities, As a consequence of drug approval, RHEUMATOLOGY 2004. so as to minimize the morbidity associ- manufacturers have a responsibility to ated with their uncommon occurrence. collect safety data actively and report Key words: TNF inhibitors, conges- these data to the appropriate agencies. tive heart failure, drug-induced lupus, Introduction For example, in the USA a manufactur- rheumatoid arthritis. The introduction of biologic agents to er must submit periodic safety reports specifically inhibit the pro-inflammato- to the FDA twice yearly (March and ry cytokine, tumor necrosis factor (TNF), September).