scholarly journals The Possible Role of Bruton Tyrosine Kinase (BTK) Inhibitors in the Treatment of COVID-19: A Review

2021 ◽  
pp. 100658
Author(s):  
Mitra Rezaei ◽  
Saghar Barati ◽  
Abdolreza Babamahmoodi ◽  
Farzaneh Dastan ◽  
Majid Marjani
Keyword(s):  
Tyrosine Kinase ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

scholarly journals Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Danling Gu ◽  
Hanning Tang ◽  
Jiazhu Wu ◽  
Jianyong Li ◽  
Yi Miao
Keyword(s):  
Adverse Events ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Clinical Studies ◽  
Acquired Resistance ◽  
B Cell Malignancies ◽  
Bcr Signaling ◽  
Bruton Tyrosine Kinase ◽  
Covalent Inhibitors ◽  
Btk Inhibitors

AbstractB cell receptor (BCR) signaling is involved in the pathogenesis of B cell malignancies. Activation of BCR signaling promotes the survival and proliferation of malignant B cells. Bruton tyrosine kinase (BTK) is a key component of BCR signaling, establishing BTK as an important therapeutic target. Several covalent BTK inhibitors have shown remarkable efficacy in the treatment of B cell malignancies, especially chronic lymphocytic leukemia. However, acquired resistance to covalent BTK inhibitors is not rare in B cell malignancies. A major mechanism for the acquired resistance is the emergence of BTK cysteine 481 (C481)  mutations, which disrupt the binding of covalent BTK inhibitors. Additionally, adverse events due to the off-target inhibition of kinases other than BTK by covalent inhibitors are common. Alternative therapeutic options are needed if acquired resistance or intolerable adverse events occur. Non-covalent BTK inhibitors do not bind to C481, therefore providing a potentially effective option to patients with B cell malignancies, including those who have developed resistance to covalent BTK inhibitors. Preliminary clinical studies have suggested that non-covalent BTK inhibitors are effective and well-tolerated. In this review, we discussed the rationale for the use of non-covalent BTK inhibitors and the preclinical and clinical studies of non-covalent BTK inhibitors in B cell malignancies.

scholarly journals Oral Bruton tyrosine kinase inhibitors selectively block atherosclerotic plaque–triggered thrombus formation in humans

Blood ◽  
2018 ◽  
Vol 131 (24) ◽  
pp. 2605-2616 ◽  
Author(s):  
Kristina Busygina ◽  
Janina Jamasbi ◽  
Till Seiler ◽  
Hans Deckmyn ◽  
Christian Weber ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Atherosclerotic Plaque ◽  
Kinase Inhibitors ◽  
Thrombus Formation ◽  
Drug Dosing ◽  
Key Points ◽  
Bruton Tyrosine Kinase ◽  
Platelet Thrombus ◽  
Btk Inhibitors

Key Points Btk inhibitors specifically block platelet thrombus formation on atherosclerotic plaque but spare physiologic hemostasis. Irreversible Btk inactivation in platelets incapable of enzyme resynthesis allows low intermittent drug dosing for antiatherothrombosis.

scholarly journals Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor

2021 ◽  
Vol 28 (1) ◽  
pp. 837-841
Author(s):  
Omar Alkharabsheh ◽  
Alhareth Alsayed ◽  
Diana M. Morlote ◽  
Amitkumar Mehta
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Case Reports ◽  
Invasive Fungal Infections ◽  
Lymphocytic Leukemia ◽  
High Morbidity ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

Bruton tyrosine kinase (BTK) inhibitors have become an important therapy for untreated and previously treated patients with chronic lymphocytic leukemia (CLL). Despite improved outcomes, rare adverse events, such as invasive fungal infections, have been reported with the use of first-generation BTK inhibitors. Invasive fungal infections carry a high morbidity and mortality risk. There have been several case reports describing the association between aspergillosis and ibrutinib treatment, but none with acalabrutinib, to our knowledge. In this case report, we describe a patient with CLL who developed an intracranial Aspergillus fumigatus infection while receiving acalabrutinib.

scholarly journals Bruton Tyrosine Kinase Inhibition and Its Role as an Emerging Treatment in Pemphigus

2021 ◽  
Vol 8 ◽  
Author(s):  
Aikaterini Patsatsi ◽  
Dedee F. Murrell
Keyword(s):  
Tyrosine Kinase ◽  
Pemphigus Vulgaris ◽  
Lymphocytic Leukemia ◽  
Proof Of Concept ◽  
Phase 2 Trial ◽  
Mantle Cell ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor ◽  
New Treatment ◽  
Btk Inhibitors

Bruton Tyrosine Kinase (BTK) has a key role in multiple pathways involved in inflammation and autoimmunity. Therefore, BTK has become a new therapeutic target for a group of hematologic and autoimmune disorders. The pharmaceutical industry has invested in the clinical development of BTK inhibitors during the last decade. Ibrutinib, for example, which was the first BTK inhibitor to be used in clinical trials, has two approved indications, mantle cell lymphoma and chronic lymphocytic leukemia, and remains under evaluation for additional indications. Rillzabrutinib (PRN1008) is a new, highly potent and selective inhibitor of BTK. Early studies performed in canine pemphigus demonstrated effectiveness. A proof-of-concept, multicenter, phase 2 trial has recently showed the efficacy and safety of oral rilzabrutinib in pemphigus vulgaris. In this mini review, we present evidence regarding the mechanisms affected by BTK inhibition and the concept of BTK inhibition as an emerging new treatment in pemphigus.

32. Chronic lymphocytic leukemia patients who develop resistance to Bruton Tyrosine Kinase (BTK) inhibitors demonstrate heterogeneous patterns of clonal evolution

2018 ◽  
Vol 226-227 ◽  
pp. 48
Author(s):  
Rashmi Kanagal-Shamanna ◽  
Preetesh Jain ◽  
Keyur Patel ◽  
Carlos Bueso-Ramos ◽  
Rajyalakshmi Luthra ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Clonal Evolution ◽  
Lymphocytic Leukemia ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

scholarly journals Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma

2017 ◽  
Vol 7 (9) ◽  
pp. 1018-1029 ◽  
Author(s):  
Christian Grommes ◽  
Alessandro Pastore ◽  
Nicolaos Palaskas ◽  
Sarah S. Tang ◽  
Carl Campos ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Critical Role ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Bruton Tyrosine Kinase

scholarly journals A Review of the Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Donald C. Moore, PharmD, BCPS, BCOP, DPLA ◽  
Daniel Thompson, PharmD
Keyword(s):  
Tyrosine Kinase ◽  
B Cell ◽  
Kinase Inhibitors ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies ◽  
Bruton Tyrosine Kinase ◽  
Integral Role ◽  
Btk Inhibitors

The B-cell receptor signaling pathway plays an integral role in the proliferation and survival of malignant B cells. Targeting the B-cell receptor pathway via the inhibition of Bruton tyrosine kinase (BTK) has evolved the treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia. Currently, there are three BTK inhibitors approved by the U.S. Food and Drug Administration: ibrutinib, acalabrutinib, and zanubrutinib. This article reviews the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions, and implications for advanced practitioners of BTK inhibitors in the treatment of B-cell malignancies.

scholarly journals Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
C. Owen ◽  
N. L. Berinstein ◽  
A. Christofides ◽  
L. H. Sehn
Keyword(s):  
Tyrosine Kinase ◽  
Mantle Cell Lymphoma ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Cell Lymphoma ◽  
Comparable Efficacy ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

Mantle cell lymphoma (mcl) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (r/r) disease have a very poor prognosis. The Bruton tyrosine kinase (btk) inhibitor ibrutinib has proven to be an effective agent for patients with r/r mcl. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with r/r mcl are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with r/r mcl.

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