keyword
MENU ▼
Read by QxMD icon Read
search

Syk inhibitor

keyword
https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#1
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27899962/new-emerging-therapies-in-the-management-of-chronic-lymphocytic-leukemia
#2
Xiao-Lin Li, Ci-Xian Zhang
Chronic lymphocytic leukemia (CLL) is considered incurable despite advances in management strategies. New drugs targeting cell pathways are currently being developed for the efficient management of CLL. Various strategies involving different targets have been developed, or are currently in the developing stage. A search was conducted in the electronic database PubMed, for pre-clinical as well as clinically controlled trials reporting various strategies against CLL currently under investigation. Novel strategies included use of antibodies, small cell inhibitors, such as spleen tyrosine kinase, LYN, cyclin-dependent kinase, and histone deacetylase inhibitors...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899526/dynamic-pre-bcr-homodimers-fine-tune-autonomous-survival-signals-in-b-cell-precursor-acute-lymphoblastic-leukemia
#3
M Frank Erasmus, Ksenia Matlawska-Wasowska, Ichiko Kinjyo, Avanika Mahajan, Stuart S Winter, Li Xu, Michael Horowitz, Diane S Lidke, Bridget S Wilson
The pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent quantum dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions...
November 29, 2016: Science Signaling
https://www.readbyqxmd.com/read/27890932/il-10-production-by-cll-cells-is-enhanced-in-the-anergic-ighv-mutated-subset-and-associates-with-reduced-dna-methylation-of-the-il10-locus
#4
S Drennan, A D'Avola, Y Gao, C Weigel, E Chrysostomou, A J Steele, T Zenz, C Plass, P W Johnson, A P Williams, G Packham, F K Stevenson, C C Oakes, F Forconi
Chronic lymphocytic leukemias (CLL) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce IL-10. The two subsets differ in their levels of anergy, defined by low surface IgM levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27889356/role-of-ptx3-in-corneal-epithelial-innate-immunity-against-aspergillus-fumigatus-infection
#5
Jie Zhang, Guiqiu Zhao, Jing Lin, Chengye Che, Cui Li, Nan Jiang, Liting Hu, Qian Wang
Pentraxin3 (PTX3), a member of long pentraxin family, plays a non-redundant role in human humoral innate immunity. However, whether PTX3 is expressed by corneal epithelial cells and its role during corneal fungi infection has not yet been investigated. To identify the presence of PTX3 in cornea, the possible mechanisms involved in its expression, and also the effects on corneal anti-fungi innate immune response, clinic human corneal tissues and cultured human corneal epithelial cells (HCECs) were resorted. PTX3 mRNA and protein were detected in corneal samples and cultured HCECs, which was significantly up-regulated after exposing to Aspergillus fumigatus (A...
November 23, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#6
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822175/keyhole-limpet-hemocyanin-induces-innate-immunity-via-syk-and-erk-phosphorylation
#7
Kyoko Yasuda, Hideki Ushio
Hemocyanin is an extracellular respiratory protein containing copper in hemolymph of invertebrates, such as Mollusk and Arthropod. Keyhole limpet hemocyanin (KLH) is one of hemocyanins and has many years of experience for vaccine developments and immunological studies in mammals including human. However, the association between KLH and the immune systems, especially the innate immune systems, remains poorly understood. The aim of this study is to clarify the direct effects of KLH on the innate immune systems...
2016: EXCLI journal
https://www.readbyqxmd.com/read/27796369/pyk2-activates-the-nlrp3-inflammasome-by-directly-phosphorylating-asc-and-contributes-to-inflammasome-dependent-peritonitis
#8
I-Che Chung, Chun-Nan OuYang, Sheng-Ning Yuan, Hsin-Pai Li, Jeng-Ting Chen, Hui-Ru Shieh, Yu-Jen Chen, David M Ojcius, Ching-Liang Chu, Jau-Song Yu, Yu-Sun Chang, Lih-Chyang Chen
The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27792904/epstein-barr-virus-latent-membrane-protein-2a-lmp2a-enhances-il-10-production-through-the-activation-of-bruton-s-tyrosine-kinase-and-stat3
#9
Ryan Incrocci, Levi Barse, Amanda Stone, Sai Vagvala, Michael Montesano, Vijay Subramaniam, Michelle Swanson-Mungerson
Previous data demonstrate that Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 to promote the survival of LMP2A-expressing B cell lymphomas. Since STAT3 is an important regulator of IL-10 production, we hypothesized that LMP2A activates a signal transduction cascade that increases STAT3 phosphorylation to enhance IL-10. Using LMP2A-negative and -positive B cell lines, the data indicate that LMP2A requires the early signaling molecules of the Syk/RAS/PI3K pathway to increase IL-10. Additional studies indicate that the PI3K-regulated kinase, BTK, is responsible for phosphorylating STAT3, which ultimately mediates the LMP2A-dependent increase in IL-10...
January 2017: Virology
https://www.readbyqxmd.com/read/27789138/synthesis-and-optimization-of-furano-3-2-d-pyrimidines-as-selective-spleen-tyrosine-kinase-syk-inhibitors
#10
Michael Hoemann, Noel Wilson, Maria Argiriadi, David Banach, Andrew Burchat, David Calderwood, Bruce Clapham, Phil Cox, David B Duignan, Don Konopacki, Gagandeep Somal, Anil Vasudevan
A series of furano[3,2-d]pyrimidine Syk inhibitors were synthesized and optimized for their enzyme potency and selectivity versus other kinases. In addition, ADME properties were assessed and compounds were prepared with optimized profiles for in vivo experiments. Compound 23 was identified as having acceptable pharmacokinetic properties and demonstrated efficacy in a rat collagen induced arthritis model.
October 11, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27785737/pharmacokinetics-pharmacodynamics-and-safety-of-entospletinib-a-novel-psyk-inhibitor-following-single-and-multiple-oral-dosing-in-healthy-volunteers
#11
Srini Ramanathan, Julie A Di Paolo, Feng Jin, Lixin Shao, Shringi Sharma, Michelle Robeson, Brian P Kearney
BACKGROUND AND OBJECTIVES: Entospletinib is a selective, reversible, adenosine triphosphate-competitive small-molecule spleen tyrosine kinase (SYK) inhibitor that blocks B cell receptor-mediated signaling and proliferation in B lymphocytes. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of entospletinib in a double-blind, single/multiple ascending dose study in healthy volunteers. METHODS: In sequential cohorts, 120 subjects received entospletinib (25-1200 mg; fasted) as single or twice-daily oral doses for 7 days...
October 26, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27758892/e2a-pbx1-remodels-oncogenic-signaling-networks-in-b-cell-precursor-acute-lymphoid-leukemia
#12
Jesús Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C Wei, Jue Feng, Jason H Kurzer, Corina Schneidawind, Stephen Hon-Kit Wong, Michael C Bassik, Michael L Cleary
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5%-7% of pediatric and 50% of pre-B-cell receptor (preBCR(+)) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of the key oncogenic effector enzyme PLCγ2...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27756749/phosphodiesterase-4-inhibitors-have-wide-ranging-activity-in-b-cell-malignancies
#13
Jeffrey D Cooney, Ricardo C T Aguiar
Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of cyclic-AMP in lymphocytes. In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-related kinases SYK and PI3K, inhibits VEGFA secretion by tumor cells, inducing cancer cell apoptosis and blocking angiogenesis in the microenvironment. We describe the successful clinical repurposing of PDE4 inhibitors in B-cell malignancies, and propose that given their anti-inflammatory/immunomodulatory activity, these agents will suppress BCR signals without the toxicity associated with other targeted biological doublets...
October 18, 2016: Blood
https://www.readbyqxmd.com/read/27720936/mir-17-92-represses-ptprot-and-pp2a-phosphatases-and-amplifies-tonic-bcr-signaling-in-dlbcl-cells
#14
Ewa Jablonska, Patryk Gorniak, Maciej Szydlowski, Tomasz Sewastianik, Emilia Bialopiotrowicz, Anna Polak, Krzysztof Warzocha, Przemyslaw Juszczynski
B-cell receptor (BCR) signaling plays pivotal role in the pathogenesis of diffuse large B-cell lymphomas (DLBCL), and targeting the BCR pathway is a highly promising therapeutic strategy in this malignancy. Oncogenic microRNA miR-17-92 modulates multiple cellular processes such as survival, proliferation, apoptosis, angiogenesis and BCR signaling. In the present study, we identified new targets of miR-17-92, PTPROt and PP2A phosphatases, which regulate SYK and AKT activity- critical components of BCR signal transduction in DLBCL cells...
October 6, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27701922/myeloperoxidase-deficiency-enhances-zymosan-phagocytosis-associated-with-up-regulation-of-surface-expression-of-cd11b-in-mouse-neutrophils
#15
Kenta Fujimoto, Takehiro Motowaki, Naoya Tamura, Yasuaki Aratani
Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride anion. Phagocytosis is a critical event induced by neutrophils for host defense and inflammation. Interestingly, we found that MPO-deficient (MPO(-/-)) neutrophils engulfed larger amounts of zymosan than wild-type neutrophils. Blocking of the CD11b subunit of complement receptor 3 (CR3) as well as inhibition of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) dramatically reduced zymosan phagocytosis...
October 4, 2016: Free Radical Research
https://www.readbyqxmd.com/read/27697994/the-dual-syk-jak-inhibitor-cerdulatinib-antagonises-b-cell-receptor-and-microenvironmental-signaling-in-chronic-lymphocytic-leukemia
#16
Matthew D Blunt, Stefan Koehrer, Rachel Dobson, Marta Larrayoz, Sarah Wilmore, Alice Hayman, Jack Parnell, Lindsay D Smith, Andrew Davies, Peter Wm Johnson, Pamela B Conley, Anjali Pandey, Jonathan C Strefford, Freda K Stevenson, Graham Packham, Francesco Forconi, Greg P Coffey, Jan Burger, Andrew J Steele
PURPOSE: B-cell receptor (BCR)-associated kinase inhibitors such as ibrutinib have revolutionised the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative and resistance is already emerging in a proportion of patients. Interleukin-4 (IL-4), expressed in CLL lymph nodes, can augment BCR-signalling and reduce the effectiveness of BCR-kinase inhibitors. Therefore simultaneous targeting of the IL-4- and BCR-signalling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients...
October 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27678281/ligand-based-and-e-pharmacophore-modeling-3d-qsar-and-hierarchical-virtual-screening-to-identify-dual-inhibitors-of-spleen-tyrosine-kinase-syk-and-janus-kinase-3-jak3
#17
Maninder Kaur, Om Silakari
The clinical efficacy of multiple kinase inhibitors has caught the interest of Pharmaceutical and Biotech researchers to develop potential drugs with multi-kinase inhibitory activity for complex diseases. In the present work, we attempted to identify dual inhibitors of. Syk and JAK3, keys players in immune signaling, by developing ideal pharmacophores integrating Ligand based pharmacophore models (LBPMs) and Structure based pharmacophore models (SBPMs), thereby projecting the optimum pharmacophoric required for inhibition of both the kinases...
September 28, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27664170/induction-of-cyclooxygenase-2-gene-by-candida-albicans-through-egfr-erk-and-p38-pathways-in-human-urinary-epithelium
#18
Shao-Hung Wang, Shou-Chieh Wang, Pei-Ching Chen, Shou-Tsung Wang, Yi-Wen Liu
In the present data, we found that Candida albicans (C. albicans) caused bladder epithelial cell morphology alteration, cell damage, and inflammatory responses, including cyclooxygenase-2 (COX-2) gene and protein expression as well as prostaglandin E2 accumulation. In addition, the molecular pathway underlying C. albicans-induced urothelial COX-2 gene expression was examined. Among MAPK pathways, phosphorylation of ERK1/2, p38, and JNK each increased following C. albicans infection for 12 h. However, C. albicans-induced COX-2 protein expression was inhibited by specific inhibitors of ERK and p38 (U0126 and SB203580) but not by JNK inhibitor SP600125...
September 23, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27592080/pleurotus-citrinopileatus-polysaccharide-induces-activation-of-human-dendritic-cells-through-multiple-pathways
#19
Ken-Ichiro Minato, Lisa C Laan, Akihiro Ohara, Irma van Die
Many edible mushrooms have become attractive as "health foods" and as source materials for immunomodulators. To increase our insight in the immune-modulatory properties of a polysaccharide of the oyster mushroom Pleurotus citrinopileatus, PCPS, we analyzed its effects on the function of human dendritic cells (DCs). We showed that PCPS induces upregulation of the surface maturation markers CD80, CD86 and HLA-DR on DCs, indicating its potential to induce DC maturation. In addition, PCPS stimulates DCs to secrete the pro-inflammatory cytokines TNF, IL-1β, IL-6 and IL-12, as well as the anti-inflammatory cytokine IL-10, and induces enhanced mRNA levels of the chemokines CCL2, CCL3, CCL8, CXCL9, CXCL10, and LTA...
September 1, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27578246/optimisation-of-a-novel-series-of-potent-and-orally-bioavailable-azanaphthyridine-syk-inhibitors
#20
Neil S Garton, Michael D Barker, Rob P Davis, Clement Douault, Edward Hooper-Greenhill, Emma Jones, Huw D Lewis, John Liddle, Dave Lugo, Scott McCleary, Alex G S Preston, Cesar Ramirez-Molina, Margarete Neu, Tracy J Shipley, Don O Somers, Robert J Watson, David M Wilson
The optimisation of the azanaphthyridine series of Spleen Tyrosine Kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over hERG activity. A good pharmacokinetic profile was achieved by modification of the pKa. Morpholine compound 32 is a potent SYK inhibitor showing moderate selectivity, good oral bioavailability and good efficacy in the rat Arthus model but demonstrated a genotoxic potential in the Ames assay...
October 1, 2016: Bioorganic & Medicinal Chemistry Letters
keyword
keyword
7247
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"