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https://www.readbyqxmd.com/read/30037618/plerixafor-and-related-macrocyclic-amines-are-potential-drug-candidates-in-treatment-of-malaria-by-filling-the-flap-region-of-plasmepsin-enzymes
#1
Ardavan Abiri
Death by Plasmodium falsiparum, the leading cause of malaria, is going to remain a major obstacle among the infectious diseases. Plasmepsin aspartic proteases are key proteins in the pathogenesis of plasmodium species which break down the hemoglobin and exploit it as a source of amino acids. These enzymes are one of the favorite targeting agents for medicinal chemists to design new drugs. Plasmepsin proteins show a "flap" region in their N-terminal domain, predisposing them to a good "filler" drug with an exceptional affinity to this enzyme...
September 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29461034/inhibition-of-hiv-fusion-by-small-molecule-agonists-through-efficacy-engineering-of-cxcr4
#2
Christian Berg, Viktorija Daugvilaite, Anne Steen, Astrid Sissel Jørgensen, Jon Våbenø, Mette Marie Rosenkilde
CXC chemokine receptor 4 (CXCR4) is involved in multiple physiological and pathological processes, notably as a coreceptor for human immunodeficiency virus (HIV) cell entry. Its broad expression pattern and vital biological importance make CXCR4 a troublesome drug target, as disruption of the interaction with its endogenous ligand, CXC chemokine ligand 12 (CXCL12), has severe consequences. In fact, only one CXCR4 drug, the bicyclam antagonist and HIV entry inhibitor AMD3100 (Plerixafor/Mozobil), has been approved for clinical use, however only for stem cell mobilization-a consequence of CXCR4 antagonism...
April 20, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/28894310/chemical-stability-of-plerixafor-after-opening-of-single-use-vial
#3
Jack T Seki, Andrea Bozovic, Roy Lee, Rita Kwong, Eshetu G Atenafu, Anna Xu, Jin-Hyeun Huh
BACKGROUND: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use...
July 2017: Canadian Journal of Hospital Pharmacy
https://www.readbyqxmd.com/read/28455878/impact-of-plerixafor-mozobil-on-hospital-efficiency-a-single-center-experience
#4
Nabih Azar, Maya Ouzegdouh, Sylvain Choquet, Véronique Leblond
Plerixafor (Mozobil) in combination with granulocyte colony-stimulating factor (G-CSF) has shown to increase mobilization of peripheral blood stem cells (PBSC) as compared to G-CSF alone in patients undergoing autologous stem cell transplantation (ASCT). However, up to 25% of patients treated with G-CSF alone still fail mobilization. Adding plerixafor to poor mobilizers allows to rescue these patients from mobilization failure and to reduce the number of apheresis sessions. The goal of this retrospective study was to capture the impact of plerixafor on treatment outcome and on apheresis department efficiency...
February 2018: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/27578423/collection-of-hematopoietic-cd34-stem-cells-in-rhesus-macaques-using-spectra-optia
#5
Lynn D Haynes, Jennifer Coonen, Jennifer Post, Kevin Brunner, Debra Bloom, Peiman Hematti, Dixon B Kaufman
BACKGROUND: Nonhuman primates, particularly rhesus macaques, are ideal preclinical large animal models to investigate organ tolerance induction protocols using donor hematopoietic stem cells (HSCs) to induce chimerism. Their relatively small size poses some challenges for the safe and effective collection of peripheral blood HSCs through apheresis procedures. We describe our experiences using the Spectra Optia apheresis unit to successfully obtain HSCs from mobilized peripheral blood of rhesus macaques...
October 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/26886512/amd3100-a-versatile-platform-for-cxcr4-targeting-68-ga-based-radiopharmaceuticals
#6
Sophie Poty, Eleni Gourni, Pauline Désogère, Frédéric Boschetti, Christine Goze, Helmut R Maecke, Franck Denat
CXCR4 is a G protein-coupled receptor (GPCR), which is overexpressed in numerous diseases, particularly in multiple cancers. Therefore, this receptor represents a valuable target for imaging and therapeutic purposes. Among the different approaches, which were developed for CXCR4 imaging, a CXCR4 antagonist biscyclam system (AMD3100, also called Mozobil), currently used in the clinic for the mobilization of hematopoietic stem cells, was radiolabeled with different radiometals such as (62)Zn, (64)Cu, (67)Ga, or (99m)Tc...
March 16, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/26646452/ulocuplumab-bms-936564-mdx1338-a-fully-human-anti-cxcr4-antibody-induces-cell-death-in-chronic-lymphocytic-leukemia-mediated-through-a-reactive-oxygen-species-dependent-pathway
#7
Manoj K Kashyap, Deepak Kumar, Harrison Jones, Carlos I Amaya-Chanaga, Michael Y Choi, Johanna Melo-Cardenas, Amine Ale-Ali, Michelle R Kuhne, Peter Sabbatini, Lewis J Cohen, Suresh G Shelat, Laura Z Rassenti, Thomas J Kipps, Pina M Cardarelli, Januario E Castro
The CXCR4 receptor (Chemokine C-X-C motif receptor 4) is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). The CXCR4 ligand (CXCL12) stimulates CXCR4 promoting cell survival and proliferation, and may contribute to the tropism of leukemia cells towards lymphoid tissues. Therefore, strategies targeting CXCR4 may constitute an effective therapeutic approach for CLL. To address that question, we studied the effect of Ulocuplumab (BMS-936564), a fully human IgG4 anti-CXCR4 antibody, using a stroma--CLL cells co-culture model...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26600122/the-interaction-of-mozobil%C3%A2-with-carboxylates
#8
Valeria Amendola, Greta Bergamaschi, Luigi Fabbrizzi, Maurizio Licchelli, Carlo Mangano
Mozobil(™) (1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane], 1, also known as JM3100 and AMD 3100) is a specific antagonist of the chemokine coreceptor CXCR4 and favours the mobilisation from the bone marrow of stem cells, which can be used for autologous transplantation. It is believed that the interaction, of both hydrogen bonding and electrostatic nature, involves a partly protonated form of Mozobil(™), LHn(n+) and the COO(-) groups of Asp(171) and Asp(262) residues protruding from the walls of the pocket of the membrane protein CXCR4...
January 21, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/26303343/plerixafor-mozobil-a-stem-cell-mobilizing-agent-for-transplantation-in-lymphoma-patients-predicted-to-be-poor-mobilizers-a-pilot-study
#9
Ivetta Danylesko, Rina Sareli, Nira Varda-Bloom, Ronit Yerushalmi, Noga Shem-Tov, Avichai Shimoni, Arnon Nagler
Autologous hematopoietic stem cell transplantation is the standard therapy for refractory/relapsed aggressive lymphoma. The initial step of the procedure involves mobilization and collection of hematopoietic stem cells. G-CSF fails to achieve mobilization in 15-25% of lymphoma patients. Plerixafor is a novel CXCR4 antagonist that can promote mobilization. It has been used successfully in patients after the failure of G-CSF. It is reasonable to test whether plerixafor should become the mobilizing agent of choice in patients expected to exhibit difficulties in mobilization...
2016: Acta Haematologica
https://www.readbyqxmd.com/read/25159162/pharmacological-intervention-at-ccr1-and-ccr5-as-an-approach-for-cancer-help-or-hindrance
#10
REVIEW
Angela Karash, Maria R Mazzoni, Annette Gilchrist
While a number of agents directed at chemokine receptors have entered clinic trials, the vast majority of these have failed, and the enthusiasm for this class of drugs has been attenuated. To date, there are two drugs that inhibit chemokine receptors approved by the FDA. The first to be approved in 2007 was maraviroc (brand name Selzentry, or Celsentri outside the US) which targets CCR5 and is used for the treatment of HIV infection. The second is plerixafor (Mozobil) which was approved in 2008, targets CXCR4, and is used for the mobilization of hematopoietic stem cells...
2014: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/25080523/cxcr%C3%A2-antagonism-as-a-therapeutic-approach-to-prevent-acute-kidney-injury
#11
A Zuk, M Gershenovich, Y Ivanova, R T MacFarland, S P Fricker, S Ledbetter
We examined whether antagonism of the CXCR₄receptor ameliorates the loss of renal function following ischemia-reperfusion. CXCR₄is ubiquitously expressed on leukocytes, known mediators of renal injury, and on bone marrow hematopoietic stem cells (HSCs). Plerixafor (AMD3100, Mozobil) is a small-molecule CXCR₄antagonist that mobilizes HSCs into the peripheral blood and also modulates the immune response in in vivo rodent models of asthma and rheumatoid arthritis. Treatment with plerixafor before and after ischemic clamping ameliorated kidney injury in a rat model of bilateral renal ischemia-reperfusion...
October 1, 2014: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/24244025/differences-in-the-phenotype-cytokine-gene-expression-profiles-and-in-vivo-alloreactivity-of-t-cells-mobilized-with-plerixafor-compared-with-g-csf
#12
COMPARATIVE STUDY
Andreas Lundqvist, Aleah L Smith, Yoshiyuki Takahashi, Susan Wong, Erkut Bahceci, Lisa Cook, Catalina Ramos, Abdul Tawab, J Philip McCoy, Elizabeth J Read, Hanh M Khuu, Charles D Bolan, Jungnam Joo, Nancy Geller, Susan F Leitman, Gary Calandra, Cynthia Dunbar, Roger Kurlander, Richard W Childs
Plerixafor (Mozobil) is a CXCR4 antagonist that rapidly mobilizes CD34(+) cells into circulation. Recently, plerixafor has been used as a single agent to mobilize peripheral blood stem cells for allogeneic hematopoietic cell transplantation. Although G-CSF mobilization is known to alter the phenotype and cytokine polarization of transplanted T cells, the effects of plerixafor mobilization on T cells have not been well characterized. In this study, we show that alterations in the T cell phenotype and cytokine gene expression profiles characteristic of G-CSF mobilization do not occur after mobilization with plerixafor...
December 15, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24179473/successful-mobilization-intra-apheresis-recruitment-and-harvest-of-hematopoietic-progenitor-cells-by-addition-of-plerixafor-and-subsequent-large-volume-leukapheresis
#13
Andreas Humpe, Ute Buwitt-Beckmann, Natalie Schub, Martin Gramatzki, Andreas Günther
BACKGROUND: In patients failing successful conventional mobilization of hematopoietic progenitor cells (HPC) plerixafor (Mozobil(®)) seems to be an alternative. We report a series of 14 patients with multiple myeloma or NHL successfully mobilized and harvested by plerixafor together with large-volume leukaphereses (LVL). METHODS: In a first series (GI), 5 patients were mobilized with G-CSF and plerixafor. In the second series (GII), 9 patients were mobilized by chemotherapy, G-CSF, and plerixafor...
August 2013: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/23830185/mobilization-of-hematopoietic-stem-cells-by-plerixafor-alone-in-children-a-sequential-bayesian-trial
#14
Fanny Chambon, Etienne Merlin, Emmanuelle Rochette, Bruno Pereira, Pascale Halle, François Deméocq, Justyna Kanold
BACKGROUND: The rapid kinetics of hematopoietic stem cells induced by Plerixafor (Mozobil®, Genzyme) should be of particular interest in children. We therefore conducted a prospective trial to determine whether a one-day mobilization by plerixafor alone was efficient enough in children with cancer. METHODS: Children with solid malignancies were consecutively recruited for this phase-IIA, Bayesian single-center prospective study. Mobilization consisted in one subcutaneous injection of 240 μg plerixafor/kg body weight at 8a...
December 2013: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/23582743/plerixafor-mozobil-and-other-mobilizing-agents
#15
REVIEW
Luca Pierelli, Paolo Perseghin
No abstract text is available yet for this article.
April 2013: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/22376154/cxcr4-inhibitors-tumor-vasculature-and-therapeutic-challenges
#16
REVIEW
Filomena de Nigris, Concetta Schiano, Teresa Infante, Claudio Napoli
CXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue and is involved in the outgrowth and metastasis of CXCR4 expressing tumors. Recent investigations have indicated that CXCL12 levels increase after chemo- and anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has emerged as a potential additional or alternative target for neo-adjuvant treatments. We have reviewed recent patent applications between 2008 and 2011 in tumor angiogenesis and the most clinical data supporting the potential use of anti-CXCR4 agents in this field...
September 2012: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/21966213/successful-mobilization-of-peripheral-blood-stem-cells-in-children-with-cancer-using-plerixafor-mozobil-and-granulocyte-colony-stimulating-factor
#17
Boryana E Avramova, Maya N Yordanova, Dobrin N Konstantinov, Dragan G Bobev
This paper describes the successful mobilization of peripheral blood stem cells for autologous transplantation in three children with malignant diseases by using plerixafor (Mozobil; Genzyme Corporation, Cambridge, MA) and granulocyte-colony stimulating factor (G-CSF) after failed previous mobilizations. A median sixfold increase in the number of circulating CD34+ cells after plerixafor treatment as compared with the baseline level was observed. An optimal CD34+ cell count for transplantation with one or two leukapheresis sessions was achieved...
2011: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/21890643/the-cxcr4-antagonist-plerixafor-corrects-panleukopenia-in-patients-with-whim-syndrome
#18
David H McDermott, Qian Liu, Jean Ulrick, Nana Kwatemaa, Sandra Anaya-O'Brien, Scott R Penzak, Joao Oliveira Filho, Debra A Long Priel, Corin Kelly, Mary Garofalo, Patricia Littel, Martha M Marquesen, Diane Hilligoss, Rosamma Decastro, Thomas A Fleisher, Douglas B Kuhns, Harry L Malech, Philip M Murphy
WHIM syndrome is a rare congenital immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (neutropenia because of impaired egress from the BM); most patients also have severe panleukopenia. Because WHIM syndrome is caused by mutations in the chemokine receptor CXCR4 that result in increased agonist-dependent signaling, we hypothesized that the CXCR4 antagonist plerixafor (Mozobil [Genyzme Corporation], AMD3100), might be an effective treatment. To test this, we enrolled 3 unrelated adult patients with the most common WHIM mutation, CXCR4(R334X), in a phase 1 dose-escalation study...
November 3, 2011: Blood
https://www.readbyqxmd.com/read/21861545/plerixafor-a-review-of-its-use-in-stem-cell-mobilization-in-patients-with-lymphoma-or-multiple-myeloma
#19
REVIEW
Gillian M Keating
Plerixafor (Mozobil®) is a CXCR4 chemokine receptor antagonist that is indicated for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the peripheral blood for collection and subsequent autologous stem-cell transplantation in patients who have non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) [US] and in patients who have lymphoma or MM and are poor mobilizers (EU). This article reviews the clinical efficacy and tolerability of subcutaneous plerixafor for stem-cell mobilization in patients with lymphoma or MM, as well as summarizing its pharmacological properties...
August 20, 2011: Drugs
https://www.readbyqxmd.com/read/21506920/clinical-and-genetic-features-of-warts-hypogammaglobulinemia-infections-and-myelokathexis-whim-syndrome
#20
REVIEW
L Dotta, L Tassone, R Badolato
WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL12 (also known as SDF-1). The altered CXCR4/CXCL12 interaction likely impairs cellular homeostasis and trafficking, resulting in immunological dysfunctions. The acronym WHIM resumes the main features of the syndrome: Warts, Hypogammaglobulinemia, Infections and Myelokathexis, which is abnormal retention of mature neutrophils in the bone marrow...
June 2011: Current Molecular Medicine
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