keyword
MENU ▼
Read by QxMD icon Read
search

Bruton tyrosine kinase

keyword
https://www.readbyqxmd.com/read/29029010/call-for-action-invasive-fungal-infections-associated-with-ibrutinib-and-other-small-molecule-kinase-inhibitors-targeting-immune-signaling-pathways
#1
Georgios Chamilos, Michail S Lionakis, Dimitrios P Kontoyiannis
Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase...
September 27, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28993409/malt1-inhibition-is-efficacious-in-both-na%C3%A3-ve-and-ibrutinib-resistant-chronic-lymphocytic-leukemia
#2
Nakhle S Saba, Deanna H Wong, Georges Tanios, Jessica R Iyer, Patricia Lobelle-Rich, Eman L Dadashian, Delong Liu, Lorena Fontan, Erik K Flemington, Cydney M Nichols, Chingiz Underbayev, Hana Safah, Ari Melnick, Adrian Wiestner, Sarah E M Herman
The clinical efficacy displayed by ibrutinib in chronic lymphocytic leukemia (CLL) has been challenged by the frequent emergence of resistant clones. The ibrutinib target, Bruton's tyrosine kinase (BTK), is essential for B cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK. Recent findings show that MI-2, a small molecule inhibitor of the para-caspase MALT1, is effective in preclinical models of another type of BCR pathway-dependent lymphoma...
October 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28978845/treatment-for-mantle-cell-lymphoma
#3
Koji Izutsu
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by CD5+, CCND1+, and the CCND1-IGH translocation. Although patients with MCL respond, at least temporarily, to conventional chemotherapy, they eventually have a relapse and the prognosis is generally poor. As a primary treatment option for patients with untreated MCL, a rituximab-containing chemotherapy regimen is administered according to the patient's eligibility for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28972595/ibrutinib-modulates-the-immunosuppressive-cll-microenvironment-through-stat3-mediated-suppression-of-regulatory-b-cell-function-and-inhibition-of-the-pd-1-pd-l1-pathway
#4
K Kondo, H Shaim, P A Thompson, J A Burger, M Keating, Z Estrov, D Harris, E Kim, A Ferrajoli, M Daher, R Basar, M Muftuoglu, N Imahashi, A Alsuliman, C Sobieski, E Gokdemir, W Wierda, N Jain, E Liu, E J Shpall, K Rezvani
Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naïve CLL. Besides directly inhibiting BTK, ibrutinib possesses immunomodulatory properties through targeting multiple signaling pathways. Understanding how this ancillary property of ibrutinib modifies the CLL microenvironment is crucial for further exploration of immune responses in this disease and devising future combination therapies. Here, we investigated the mechanisms underlying the immunomodulatory properties of ibrutinib...
October 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28953011/self-limiting-ibrutinib-induced-neutrophilic-panniculitis
#5
Jacob Stewart, Stephanie Bayers, Travis Vandergriff
Neutrophilic panniculitis is a relatively rare condition, characterized by predominantly neutrophilic inflammation in the subcutaneous fat. Rarely, neutrophilic panniculitis may be induced by chemotherapeutics or targeted molecular therapies, including the Bruton tyrosine kinase inhibitor ibrutinib. Previously reported cases of ibrutinib-induced panniculitis were suppressed with sustained low-dose steroid therapy while continuing ibrutinib therapy. To our knowledge, self-limiting panniculitis during ibrutinib therapy has not yet been described...
September 20, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28951258/ibrutinib-suppresses-alloantibody-responses-in-a-mouse-model-of-allosensitization
#6
Irene Kim, Gordon Wu, Ning-Ning Chai, Andrew S Klein, Stanley Jordan
BACKGROUND: Ibrutinib is a Bruton's tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling. Complete BTK deficiency is associated with absence of B-cells. Ibrutinb is currently approved by FDA for treatment of B-cell malignancies, including Waldenström macroglobulinaemia. We recently carried out studies to determine if ibrutinib could modify alloantibody responses. MATERIALS AND METHODS: A mouse model of allogenic sensitization using a C57BL/6 mouse as the recipient of a skin allograft from an HLA-A2 transgenic mouse was utilized to examine the effects of ibrutinib on alloantibody responses and B cell effector functions...
September 23, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28950886/hm71224-a-selective-bruton-s-tyrosine-kinase-inhibitor-attenuates-the-development-of-murine-lupus
#7
Yu-Yon Kim, Ki Tae Park, Sun Young Jang, Kyu Hang Lee, Joo-Yun Byun, Kwee Hyun Suh, Young-Mi Lee, Young Hoon Kim, Kwang Woo Hwang
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with B cell hyperactivity, and lupus nephritis (LN), in particular, is promoted by the production of autoantibodies and immune complex deposition. Bruton's tyrosine kinase (BTK) plays critical roles in B cell receptor-related and Fc receptor-related signaling. We aimed to investigate the impact of therapeutic intervention with HM71224 (LY3337641), a selective BTK inhibitor, on the development of murine SLE-like disease features...
September 26, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28947935/bruton-s-tyrosine-kinase-inhibitors-for-the-treatment-of-autoimmune-diseases-and-cancers
#8
EDITORIAL
Robert B Kargbo
No abstract text is available yet for this article.
September 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28946903/high-expression-of-bruton-s-tyrosine-kinase-btk-is-required-for-egfr-induced-nf-%C3%AE%C2%BAb-activation-and-predicts-poor-prognosis-in-human-glioma
#9
Chenglong Yue, Mingshan Niu, Qian Qian Shan, Ting Zhou, Yiming Tu, Peng Xie, Lei Hua, Rutong Yu, Xuejiao Liu
BACKGROUND: Malignant glioma is the most common primary brain tumor in adults and has a poor prognosis. However, there are no effective targeted therapies for glioma patients. Thus, the development of novel targeted therapeutics for glioma is urgently needed. METHODS: In this study, we examined the prognostic significance BTK expression in patients with glioma. Furthermore, we investigated the mechanism and therapeutic potential of ibrutinib in the treatment of human glioma in vitro and in vivo...
September 25, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28942659/novel-synthetic-drugs-currently-in-clinical-development-for-chronic-lymphocytic-leukemia
#10
Pawel Robak, Tadeusz Robak
Over the last few years, several new synthetic drugs, particularly Bruton's tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K) and BCL-2 inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). Areas covered: This review highlights key aspects of BTK, PI3K and BCL-2 inhibitors that are currently at various stages of preclinical and clinical development in CLL. A literature review of the MEDLINE database for articles in English concerning CLL, B-cell receptor, BCL-2 antagonists, BTK inhibitors and PI3K inhibitors, was conducted via PubMed...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28924018/ibrutinib-for-chronic-graft-versus-host-disease-after-failure-of-prior-therapy
#11
David Miklos, Corey S Cutler, Mukta Arora, Edmund K Waller, Madan Jagasia, Iskra Pusic, Mary E Flowers, Aaron C Logan, Ryotaro Nakamura, Bruce R Blazar, Yunfeng Li, Stephen Chang, Indu Lal, Jason Dubovsky, Danelle F James, Lori Styles, Samantha Jaglowski
Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few effective options available after failure of corticosteroids. B and T cells play a role in the pathophysiology of cGVHD. Ibrutinib inhibits Bruton's tyrosine kinase in B cells and interleukin-2-inducible T-cell kinase in T cells. In preclinical models, ibrutinib reduced severity of cGVHD. This multicenter, open-label study evaluated the safety and efficacy of ibrutinib in patients with active cGVHD with inadequate response to corticosteroid-containing therapies...
September 18, 2017: Blood
https://www.readbyqxmd.com/read/28905990/the-mtor-kinase-inhibitor-everolimus-synergistically-enhances-the-anti-tumor-effect-of-the-bruton-s-tyrosine-kinase-btk-inhibitor-pls-123-on-mantle-cell-lymphoma
#12
Jiao Li, Xiaogan Wang, Yan Xie, Zhitao Ying, Weiping Liu, Lingyan Ping, Chen Zhang, Zhengying Pan, Ning Ding, Yuqin Song, Jun Zhu
Mantle cell lymphoma (MCL) is an aggressive and incurable malignant disease. Despite of general chemotherapy, relapse and mortality are common, highlighting the need for the development of novel targeted drugs or combination of therapeutic regimens. Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28901789/cardiac-side-effects-of-bruton-tyrosine-kinase-btk-inhibitors
#13
Chloe Pek Sang Tang, Julie McMullen, Constantine Tam
The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects...
September 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28882879/acalabrutinib-acp-196-a-covalent-bruton-tyrosine-kinase-inhibitor-with-a-differentiated-selectivity-and-in-vivo-potency-profile
#14
Tjeerd Barf, Todd Covey, Raquel Izumi, Bas van de Kar, Michael Gulrajani, Bart van Lith, Maaike van Hoek, Edwin de Zwart, Diana Mittag, Dennis Demont, Saskia Verkaik, Fanny Krantz, Paul G Pearson, Roger Ulrich, Allard Kaptein
Several small-molecule Bruton tyrosine kinase (BTK) inhibitors are in development for B cell malignancies and autoimmune disorders, each characterized by distinct potency and selectivity patterns. Herein we describe the pharmacologic characterization of BTK inhibitor acalabrutinib [compound 1, ACP-196 (4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-(2-pyridyl)benzamide)]. Acalabrutinib possesses a reactive butynamide group that binds covalently to Cys481 in BTK. Relative to the other BTK inhibitors described here, the reduced intrinsic reactivity of acalabrutinib helps to limit inhibition of off-target kinases having cysteine-mediated covalent binding potential...
November 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28867612/achieving-a-graded-immune-response-btk-adopts-a-range-of-active-inactive-conformations-dictated-by-multiple-interdomain-contacts
#15
Raji E Joseph, Thomas E Wales, D Bruce Fulton, John R Engen, Amy H Andreotti
Capturing the functionally relevant forms of dynamic, multidomain proteins is extremely challenging. Bruton's tyrosine kinase (BTK), a kinase essential for B and mast cell function, has stubbornly resisted crystallization in its full-length form. Here, nuclear magnetic resonance and hydrogen-deuterium exchange mass spectrometry show that BTK adopts a closed conformation in dynamic equilibrium with open, active conformations. BTK lacks the phosphotyrosine regulatory tail of the SRC kinases, yet nevertheless achieves a phosphotyrosine-independent C-terminal latch...
October 3, 2017: Structure
https://www.readbyqxmd.com/read/28864640/spotlight-on-ibrutinib-in-pcnsl-adding-another-feather-to-its-cap
#16
Aparna Lakshmanan, John C Byrd
In this issue Grommes and colleagues elegantly show that the irreversible inhibitor of Bruton tyrosine kinase, ibrutinib, promotes a high proportion of durable responses in primary central nervous system lymphoma, a type of diffuse large B-cell lymphoma (DLBCL), and also in secondary DLBCL relapsing to the central nervous system. Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease...
September 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28829205/potential-applications-of-bruton-s-tyrosine-kinase-inhibitors-for-the-prevention-of-allergic-reactions
#17
Melanie C Dispenza, Jennifer A Regan, Bruce S Bochner
No abstract text is available yet for this article.
October 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#18
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28792217/kinase-crystal-miner-a-powerful-approach-to-repurposing-3d-hinge-binding-fragments-and-its-application-to-finding-novel-bruton-tyrosine-kinase-inhibitors
#19
Prasenjit Mukherjee, Jörg Bentzien, Todd Bosanac, Wang Mao, Michael Burke, Ingo Muegge
Protein kinases represent an important target class for drug discovery because of their role in signaling pathways involved in disease areas such as oncology and immunology. A key element of many ATP-competitive kinase inhibitors is their hinge-binding motif. Here, we describe Kinase Crystal Miner (KCM)-a new approach developed at Boehringer Ingelheim (BI) that harvests the existing crystallographic information on kinase-inhibitor co-crystal structures from internal and external databases. About 1000 unique three-dimensional kinase inhibitor hinge binding motifs have been extracted from structures covering more than 180 different protein kinases...
September 25, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#20
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
keyword
keyword
24747
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"