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https://www.readbyqxmd.com/read/27801778/antiviral-screening-of-multiple-compounds-against-ebola-virus
#1
Stuart D Dowall, Kevin Bewley, Robert J Watson, Seshadri S Vasan, Chandradhish Ghosh, Mohini M Konai, Gro Gausdal, James B Lorens, Jason Long, Wendy Barclay, Isabel Garcia-Dorival, Julian Hiscox, Andrew Bosworth, Irene Taylor, Linda Easterbrook, James Pitman, Sian Summers, Jenny Chan-Pensley, Simon Funnell, Julia Vipond, Sue Charlton, Jayanta Haldar, Roger Hewson, Miles W Carroll
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests...
October 27, 2016: Viruses
https://www.readbyqxmd.com/read/27243433/providing-unused-medications-at-discharge-dosing-error-with-tasigna
#2
Ann Shastay
No abstract text is available yet for this article.
June 2016: Home Healthcare Now
https://www.readbyqxmd.com/read/26283632/nilotinib-tasigna%C3%A2-in-the-treatment-of-early-diffuse-systemic-sclerosis-an-open-label-pilot-clinical-trial
#3
Jessica K Gordon, Viktor Martyanov, Cynthia Magro, Horatio F Wildman, Tammara A Wood, Wei-Ti Huang, Mary K Crow, Michael L Whitfield, Robert F Spiera
INTRODUCTION: Tyrosine kinase inhibitors (TKI) are medications of interest in the treatment of Systemic Sclerosis (SSc) because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous (dc)SSc with the TKI nilotinib (Tasigna™). METHODS: Ten adult patients with early dcSSc were treated with nilotinib...
August 18, 2015: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/25984303/possible-fda-approved-drugs-to-treat-ebola-virus-infection
#4
Shu Yuan
There is currently no effective treatment for the Ebola virus (EBOV) thus far. Most drugs and vaccines developed to date have not yet been approved for human trials. Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna block the release of viral particles; however, their clinical dosages are much lower than the dosages required for effective EBOV suppression. An α-1,2-glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly and secretion. Additionally, the estrogen receptor modulators Clomiphene and Toremifene prevent membrane fusion of EBOV and 50-90% of treated mice survived after Clomiphene/Toremifene treatments...
2015: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/25698901/the-effect-of-nilotinib-plus-arsenic-trioxide-on-the-proliferation-and-differentiation-of-primary-leukemic-cells-from-patients-with-chronic-myoloid-leukemia-in-blast-crisis
#5
Wei Wang, Fei-Fei Lv, Yan Du, Nannan Li, YaLing Chen, LiHong Chen
AIM: To determine the effects of arsenic trioxide (ATO) and nilotinib (AMN107, Tasigna) alone or in combination on the proliferation and differentiation of primary leukemic cells from patients with chronic myeloid leukemia in the blast crisis phase (CML-BC). METHODS: Cells were isolated from the bone marrow of CML-BC patients and were treated with 1 μM ATO and 5 nM nilotinib, either alone or in combination. Cell proliferation was evaluated using a MTT assay. Cell morphology and the content of hemoglobin were examined with Wright-Giemsa staining and benzidine staining, respectively...
2015: Cancer Cell International
https://www.readbyqxmd.com/read/25477591/decimal-commas-are-a-problem-actiq-is-not-for-sore-throats-dosing-error-with-tasigna-repackaging-of-imbruvica-is-approved
#6
Michael R Cohen, Judy L Smetzer
These medication errors have occurred in health care facilities at least once. They will happen again-perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program...
September 2014: Hospital Pharmacy
https://www.readbyqxmd.com/read/25202051/liposomes-ameliorate-crizotinib-and-nilotinib-induced-inhibition-of-the-cardiac-ikr-channel-and-qtc-prolongation
#7
George M Shopp, Lawrence Helson, Annie Bouchard, Dany Salvail, Muhammad Majeed
Crizotinib (Xalkori®) and nilotinib (Tasigna®) are tyrosine kinase inhibitors approved for the treatment of non-small cell lung cancer and chronic myeloid leukemia, respectively. Both have been shown to result in electrocardiogram rate-corrected Q-wave T-wave interval (QTc) prolongation in humans and animals. Liposomes have been shown to ameliorate drug-induced effects on the cardiac-delayed rectifier K(+) current (IKr, KV11.1), coded by the human ether-a-go-go-related gene (hERG). This study was undertaken to determine if liposomes would also decrease the effect of crizotinib and nilotinib on the IKr channel...
September 2014: Anticancer Research
https://www.readbyqxmd.com/read/24865254/pharmacophore-modeling-of-nilotinib-as-an-inhibitor-of-atp-binding-cassette-drug-transporters-and-bcr-abl-kinase-using-a-three-dimensional-quantitative-structure-activity-relationship-approach
#8
Suneet Shukla, Abdul Kouanda, Latoya Silverton, Tanaji T Talele, Suresh V Ambudkar
Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat chronic phase chronic myeloid leukemia patients. It is also a transport substrate of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein, P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and toxicity of this drug. The goal of this study was to identify pharmacophoric features of nilotinib in order to potentially develop specific inhibitors of BCR-ABL kinase with minimal interactions with ABC drug transporters...
July 7, 2014: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/24455114/treatment-recommendations-for-chronic-myeloid-leukemia
#9
REVIEW
Michele Baccarani, Fausto Castagnetti, Gabriele Gugliotta, Francesca Palandri, Gianantonio Rosti
The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy...
January 2, 2014: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/24184819/template-based-de-novo-design-for-type-ii-kinase-inhibitors-and-its-extented-application-to-acetylcholinesterase-inhibitors
#10
Bo-Han Su, Yi-Syuan Huang, Chia-Yun Chang, Yi-Shu Tu, Yufeng J Tseng
There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template...
2013: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/23564552/-adequate-supportive-treatment-in-therapeutic-use-of-biologicals-for-gi-tumours-in-oncosurgery-what-does-the-surgeon-need-to-know
#11
REVIEW
E Kettner, H Hütten, J Ricke, F Meyer
BACKGROUND: Along with the increasing use and inauguration of novel antineoplastic substances (inhibitors, antibodies [Ab]) at various levels of the tumour cell-specific intracellular signalling (transduction cascade) on the cell surface and within the cell as well as messengers ["biologicals", "targeted therapy"]), a new quality, intensity and complexity of adverse effects was simultaneously developed, which have become more and more relevant even to oncosurgeons. AIM: A summary is given of clinically obtained expertise including recommendations for a competent approach, management and use of biologicals for targeted therapy in case of abnormal or adverse effects as well as toxic reactions, which are compared with available data from the literature and provided as systematic short review on the clinically used substances and drugs in GI tumour lesions...
April 2013: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/23175995/is-imatinib-still-an-acceptable-first-line-treatment-for-cml-in-chronic-phase
#12
John M Goldman, David Marin
The introduction of the tyrosine kinase inhibitor (TKI) imatinib (Gleevec) into clinical practice resulted in a very dramatic prolongation of survival for most, but not all, patients with chronic myeloid leukemia in chronic phase (CML-CP). A leukemia with a median survival of about 5 years was transformed into one for which the survival in many cases promises to be comparable to that of normal persons of similar age. The more recently available TKIs, namely nilotinib (Tasigna) and dasatinib (Sprycel), produce more rapid responses but have not yet shown any overall survival advantage compared with long-term administration of imatinib...
October 2012: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/22763385/nilotinib-in-imatinib-resistant-or-imatinib-intolerant-patients-with-chronic-myeloid-leukemia-in-chronic-phase-48-month-follow-up-results-of-a-phase-ii-study
#13
MULTICENTER STUDY
F J Giles, P D le Coutre, J Pinilla-Ibarz, R A Larson, N Gattermann, O G Ottmann, A Hochhaus, J P Radich, G Saglio, T P Hughes, G Martinelli, D-W Kim, S Novick, K Gillis, X Fan, J Cortes, M Baccarani, H M Kantarjian
Nilotinib (Tasigna) is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) who are newly diagnosed or intolerant of or resistant to imatinib. The 48-month follow-up data for patients with CML-CP treated with nilotinib after imatinib resistance or intolerance on an international phase II study were analyzed. Overall, 59% of patients achieved major cytogenetic response; 45% achieved complete cytogenetic response while on study...
January 2013: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/22745749/investigation-of-the-in-vitro-therapeutic-efficacy-of-nilotinib-in-immortalized-human-nf2-null-vestibular-schwannoma-cells
#14
Nesrin Sabha, Karolyn Au, Sameer Agnihotri, Sanjay Singh, Rupinder Mangat, Abhijit Guha, Gelareh Zadeh
Vestibular schwannomas (VS) are a common posterior fossa brain tumor, and though benign can cause significant morbidity, particularly loss of hearing, tinnitus, vertigo and facial paralysis. The current treatment options for VS include microsurgical resection, stereotactic radiosurgery or close surveillance monitoring, with each treatment option carrying associated complications and morbidities. Most importantly, none of these options can definitively reverse hearing loss or tinnitus. Identification of a novel medical therapy, through the use of targeted molecular inhibition, is therefore a highly desirable treatment strategy that may minimize complications arising from both tumor and treatment and more importantly be suitable for patients whose options are limited with respect to surgical or radiosurgical interventions...
2012: PloS One
https://www.readbyqxmd.com/read/22741607/a-novel-and-facile-synthetic-approach-for-tasigna
#15
Xiaoyan Pan, Wen Lu, Pengfei Li, Fang Wang, Chen Wang, Zhigang Hu, Jie Zhang
A simple and practical synthetic approach for tasigna was described here in six steps with high yield (40%). All of the intermediates and final target compound were isolated cleanly in high yield without a need for chromatographic purification. Significantly, the facile synthetic route proposed in this work has the characteristics of mild synthetic conditions, inexpensive reagents, high yield and simple operation.
September 2012: Medicinal Chemistry
https://www.readbyqxmd.com/read/22076466/nilotinib-in-patients-with-ph-chronic-myeloid-leukemia-in-accelerated-phase-following-imatinib-resistance-or-intolerance-24-month-follow-up-results
#16
P D le Coutre, F J Giles, A Hochhaus, J F Apperley, G J Ossenkoppele, R Blakesley, Y Shou, N J Gallagher, M Baccarani, J Cortes, H M Kantarjian
Nilotinib (Tasigna) is a potent and selective BCR-ABL inhibitor approved for use in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CML-CP) and in patients with CML-CP and accelerated phase (CML-AP) who are resistant to or intolerant of imatinib. Patients with CML-AP (N = 137) with at least 24 months of follow-up or who discontinued early were evaluated to determine the efficacy and tolerability of nilotinib. The majority (55%) of patients achieved a confirmed hematologic response, and 31% attained a confirmed complete hematologic response on nilotinib treatment...
June 2012: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/21727212/nilotinib-alone-or-in-combination-with-selumetinib-is-a-drug-candidate-for-neurofibromatosis-type-2
#17
Sylwia Ammoun, Marei Caroline Schmid, Joceline Triner, Paul Manley, Clemens Oliver Hanemann
Loss of the tumor suppressor merlin is a cause of frequent tumors of the nervous system, such as schwannomas, meningiomas, and ependymomas, which occur spontaneously or as part of neurofibromatosis type 2 (NF2). Because there is medical need for drug therapies for these tumors, our aim is to find therapeutic targets. We have studied the pathobiology of schwannomas, because they are the most common merlin-deficient tumors and are a model for all merlin-deficient tumors. With use of a human schwannoma in vitro model, we previously described strong overexpression/activation of platelet-derived growth factor receptor-β (PDGFR-β) leading to strong, long-lasting activation of extracellular-signal-regulated kinase (ERK1/2) and AKT and increased schwannoma growth, which we successfully inhibited using the PDGFR/Raf inhibitor sorafenib...
July 2011: Neuro-oncology
https://www.readbyqxmd.com/read/21630681/synthesis-and-characterization-of-a-bodipy-conjugate-of-the-bcr-abl-kinase-inhibitor-tasigna-nilotinib-evidence-for-transport-of-tasigna-and-its-fluorescent-derivative-by-abc-drug-transporters
#18
Suneet Shukla, Amanda P Skoumbourdis, Martin J Walsh, Anika M S Hartz, King Leung Fung, Chung-Pu Wu, Michael M Gottesman, Björn Bauer, Craig J Thomas, Suresh V Ambudkar
Tasigna (Nilotinib) is a BCR-ABL kinase inhibitor recently approved by the Food and Drug Administration, which is indicated for the treatment of drug-resistant chronic myelogenous leukemia (CML). The efflux of tyrosine kinase inhibitors by ATP-binding cassette (ABC) drug transporters, which actively pump these drugs out of cells utilizing ATP as an energy source, has been linked to the development of drug resistance in CML patients. We report here the synthesis and characterization of a fluorescent derivative of Tasigna to study its interaction with two major ABC transporters, P-glycoprotein (Pgp) and ABCG2, in in vitro and ex vivo assays...
August 1, 2011: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/21184622/effects-of-nilotinib-on-single-dose-warfarin-pharmacokinetics-and-pharmacodynamics-a-randomized-single-blind-two-period-crossover-study-in-healthy-subjects
#19
RANDOMIZED CONTROLLED TRIAL
Ophelia Q P Yin, Neil Gallagher, Deirdre Fischer, Lily Zhao, Wei Zhou, Elisabeth Leroy, Georg Golor, Horst Schran
BACKGROUND AND OBJECTIVE: Nilotinib (Tasigna®), a highly selective and potent BCR-ABL tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukaemia in the chronic phase (CML-CP) and the accelerated phase (CML-AP) in patients resistant or intolerant to prior therapy, including imatinib. Nilotinib has shown competitive inhibition of cytochrome P450 enzyme (CYP) 2C9 in vitro, but its effect on CYP2C9 activity in humans is unknown. This study evaluated the effects of nilotinib on the pharmacokinetics and pharmacodynamics of warfarin, a sensitive CYP2C9 substrate, in healthy subjects...
2011: Clinical Drug Investigation
https://www.readbyqxmd.com/read/21091142/nilotinib-is-superior-to-imatinib-as-first-line-therapy-of-chronic-myeloid-leukemia-the-enestnd-study
#20
Francis J Giles, Gianantonio Rosti, Photis Beris, Richard E Clark, Philipp le Coutre, Francois-Xavier Mahon, Juan-Luis Steegmann, Peter Valent, Giuseppe Saglio
Nilotinib (Tasigna(®)) is a more potent BCR-ABL inhibitor than imatinib and was designed to overcome imatinib's deficiencies. Nilotinib has significant efficacy in patients with chronic myeloid leukemia (CML) in chronic phase, accelerated phase and blastic phase, following imatinib failure. Based on the results of the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, the US FDA has granted accelerated approval of nilotinib for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase...
December 2010: Expert Review of Hematology
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