Read by QxMD icon Read

Bruton tyrosine kinase

Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Deepa Jeyakumar, Susan O'Brien
Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton's tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and infections) associated with chemoimmunotherapy...
March 2016: Best Practice & Research. Clinical Haematology
Atish Mohanty, Natalie Sandoval, Manasi Das, Raju Pillai, Lu Chen, Robert W Chen, Hesham M Amin, Michael Wang, Guido Marcucci, Dennis D Weisenburger, Steven T Rosen, Lan V Pham, Vu N Ngo
Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation, which leads to deregulated expression of the cell cycle regulatory protein cyclin D1 (CCND1). Genomic studies of MCL have also identified recurrent mutations in the coding region of CCND1. However, the functional consequence of these mutations is not known. Here, we showed that, compared to wild type (WT), single E36K, Y44D or C47S CCND1 mutations increased CCND1 protein levels in MCL cell lines. Mechanistically, these mutations stabilized CCND1 protein through attenuation of threonine-286 phosphorylation, which is important for proteolysis through the ubiquitin-proteasome pathway...
October 4, 2016: Oncotarget
Koh Okamoto, Laurie A Proia, Patricia L Demarais
Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation...
2016: Case Reports in Infectious Diseases
Anuj Rathi, Riyaz Syed, Vijay Singh, Han-Seung Shin, Rahul V Patel
Cancer accounts for a numbers of deaths each year. Consequently, prevention of this deadly disease though the invention of new anticancer agents is of utmost importance. The current review elaborates the importance of indole designs as patented in the form of anticancer drug-like molecules targeting different cites of biological arena, specifically kinases such as platelet-derived growth factor receptor, vascular endothelial growth factor receptor and fibroblast growth factor receptor, Bruton's tyrosine kinase, anaplastic lymphoma kinase, Janus kinase, cyclin-dependent kinase aurora kinases A, B and C, checkpoint kinases, protein kinase R, Pim kinases, phosphoinositide 3-kinase, altered proteins kinases, polo-like kinase and many more...
October 3, 2016: Recent Patents on Anti-cancer Drug Discovery
Alessandro Gozzetti, Veronica Candi, Corrado Zuanelli Brambilla, Giulia Papini, Alberto Fabbri, Monica Bocchia
Abnormality of the B-cell receptor (BCR) signaling is correlated to origin of many B-cell malignancies.. Bruton's tyrosine kinase (BTK), is described as a possible target in a many B-cell neoplasms. Ibrutinib is the most used inhibitor of BTK and has great tolerability and efficacy in chronic lymphocytic leukemia. This review summarizes results with ibrutinib in clinical trials and novel BTK inhibitors of interest.
September 28, 2016: Anti-cancer Agents in Medicinal Chemistry
Britt Van Aelst, Rosalie Devloo, Pierre Zach Eacutee, Ruben t'Kindt, Koen Sandra, Philippe Vandekerckhove, Veerle Compernolle, Hendrik B Feys
Psoralen and ultraviolet A light (PUVA) is used to kill pathogens in blood products and as a treatment of aberrant cell proliferation in dermatitis, cutaneous T-cell lymphoma and graft-versus-host-disease (GVHD). DNA damage is well described, but the direct effects of PUVA on cell signal transduction are poorly understood. Because platelets are anucleate and contain archetypal signal transduction machinery these are ideally suited to address this. Lipidomics on platelet membrane extracts showed that psoralen forms adducts with unsaturated carbon bonds of fatty acyls in all major phospholipid classes after PUVA...
September 29, 2016: Journal of Biological Chemistry
Prithviraj Bose, Varsha V Gandhi, Michael J Keating
Ibrutinib, a first-in-class covalent inhibitor of Bruton's tyrosine kinase (BTK), is approved in many countries for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and for previously untreated disease with a 17p deletion and, most recently, as a frontline therapy for CLL. In controlled trials in CLL, ibrutinib produced high response rates and improved survival in both the frontline and relapsed settings. While ibrutinib controls CLL with impressive efficacy, it only infrequently induces complete remissions, particularly of relapsed CLL, and does not eradicate minimal residual disease...
October 11, 2016: Expert Opinion on Drug Metabolism & Toxicology
Tomoko Yasuhiro, Wako Sawada, Christian Klein, Ryohei Kozaki, Shingo Hotta, Toshio Yoshizawa
The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101)...
August 9, 2016: Leukemia & Lymphoma
Jun Chen, Taisei Kinoshita, Juthamas Sukbuntherng, Betty Y Chang, Laurence Elias
Ibrutinib is a potent, small-molecule Bruton's tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (<100 nM); additionally the IC50s were lower than that of lapatinib and dacomitinib...
September 27, 2016: Molecular Cancer Therapeutics
(no author information available yet)
An article in the July 2016 issue, "Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma" by Gaurav Varma, MSPH, Tyler P. Johnson, MD, and Ranjana H. Advani, MD, described ONO/GS-4059 as a "reversible" inhibitor of BTK when it is in fact an "irreversible" inhibitor. We have made the correction to pages 546 and 552 of the online version at Many thanks to an astute reader for pointing out the error. This corrects the article pmid:27379948.
September 2016: Clinical Advances in Hematology & Oncology: H&O
Wafa A Mera, Malek Alzihlif, Mutasem O Taha, Mohammad A Khanfar
Bruton's Tyrosine Kinase (BTK) is a one of the Tec tyrosine kinase family. It has an essential role in B-cell development and function. Activation of BTK has been associated with the pathogenesis of many types of lymphomas and leukemia, and involved in non-life threatening autoimmune diseases. In this study, exhaustive pharmacophore modeling was combined with QSAR analyses to examine the structural requirements for anti-BTK activities. Genetic function algorithm (GFA) was coupled with multiple linear regression (MLR) analysis to select the best combinations of physicochemical descriptors and pharmacophoric hypothesis capable of generating predictive and self-consistent QSAR models...
September 26, 2016: Anti-cancer Agents in Medicinal Chemistry
Rebecca Voltan, Erika Rimondi, Elisabetta Melloni, Gian Matteo Rigolin, Fabio Casciano, Maria Vittoria Arcidiacono, Claudio Celeghini, Antonio Cuneo, Giorgio Zauli, Paola Secchiero
OBJECTIVE: The aim of this study was to investigate the anti-leukemic activity of the Bruton tyrosine kinase inhibitor Ibrutinib in combination with the small molecule MDM-2 inhibitor Nutlin-3 in preclinical models. METHODS: The potential efficacy of the Ibrutinib/Nutlin-3 combination was evaluated in vitro in a panel of B leukemic cell lines (EHEB, JVM-2, JVM-3, MEC-1, MEC-2) and in primary B-chronic lymphocytic leukemia (B-CLL) patient samples, by assessing cell viability, cell cycle profile, apoptosis and intracellular pathway modulations...
September 20, 2016: Oncotarget
Robert Roskoski
The Bruton non-receptor protein-tyrosine kinase (BTK), a deficiency of which leads to X-linked agammaglobulinemia, plays a central role in B cell antigen receptor signaling. Owing to the exclusivity of this enzyme in B cells, the acronym could represent B cell tyrosine kinase. BTK is activated by the Lyn and SYK protein kinases following activation of the B cell receptor. BTK in turn catalyzes the phosphorylation and activation of phospholipase Cγ2 leading to the downstream activation of the Ras/RAF/MEK/ERK pathway and the NF-κB pathways...
September 15, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Susan O'Brien, Jeffrey A Jones, Steven E Coutre, Anthony R Mato, Peter Hillmen, Constantine Tam, Anders Österborg, Tanya Siddiqi, Michael J Thirman, Richard R Furman, Osman Ilhan, Michael J Keating, Timothy G Call, Jennifer R Brown, Michelle Stevens-Brogan, Yunfeng Li, Fong Clow, Danelle F James, Alvina D Chu, Michael Hallek, Stephan Stilgenbauer
BACKGROUND: The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. METHODS: We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand...
October 2016: Lancet Oncology
Mohammad Althubiti, Miran Rada, Jesvin Samuel, Josep M Escorsa, Hishyar Najeeb, Koon-Guan Lee, Kong-Peng Lam, George D D Jones, Nickolai A Barlev, Salvador Macip
p53 is a tumor suppressor that prevents the emergence of transformed cells by inducing apoptosis or senescence, among other responses. Its functions are regulated tightly by posttranslational modifications. Here we show that Bruton's tyrosine kinase (BTK) is a novel modulator of p53. We found that BTK is induced in response to DNA damage and p53 activation. BTK induction leads to p53 phosphorylation, which constitutes a positive feedback loop that increases p53 protein levels and enhances the transactivation of its target genes in response to stress...
September 15, 2016: Cancer Research
Ki-Shuk Shim, Chung-Jo Lee, Nam-Hui Yim, Min Jung Gu, Jin Yeul Ma
Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity...
2016: American Journal of Chinese Medicine
Shruti Sharma, Natalie Galanina, Ailin Guo, Jimmy Lee, Sabah Kadri, Charles Van Slambrouck, Bradley Long, Weige Wang, Mei Ming, Larissa V Furtado, Jeremy P Segal, Wendy Stock, Girish Venkataraman, Wei-Jen Tang, Pin Lu, Y Lynn Wang
Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naïve chronic lymphocytic leukemia (CLL). However, about 25% of patients discontinue ibrutinib therapy at a median follow-up of 20 months and many patients discontinue the treatment due to leukemia progression or Richter transformation. Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance...
September 10, 2016: Oncotarget
Man Fai Law, Rita Ho, Carmen K M Cheung, Lydia H P Tam, Karen Ma, Kent C Y So, Bonaventure Ip, Jacqueline So, Jennifer Lai, Joyce Ng, Tommy H C Tam
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc)...
July 28, 2016: World Journal of Gastroenterology: WJG
Stefania Fiorcari, Rossana Maffei, Valentina Audrito, Silvia Martinelli, Elisa Ten Hacken, Patrizia Zucchini, Giulia Grisendi, Leonardo Potenza, Mario Luppi, Jan A Burger, Silvia Deaglio, Roberto Marasca
In lymphoid organs, nurse-like cells (NLCs) show properties of tumor-associated macrophages, playing a crucial role in chronic lymphocytic leukemia (CLL) cell survival. Ibrutinib, a potent inhibitor of Bruton's tyrosine kinase (BTK), is able to counteract pro-survival signals in CLL cells. Since the effects on CLL cells have been studied in the last years, less is known about the influence of ibrutinib on NLCs properties. We sought to determine how ibrutinib modifies NLCs functions focusing on the balance between immunosuppressive and inflammatory features...
September 1, 2016: Oncotarget
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"