BTK

Bruton tyrosine kinase

Gene Context Sentence


Table 2. Analysis of context sentence of BTK gene in 11 abstracts.

PMID Gene Context Sentence
32345646 As the SARS-CoV-2 (COVID19) pandemic spreads and the number of Bruton’s tyrosine kinase inhibitor (BTKi)-treated COVID19 affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. […] In favor of BTKi continuation, BTK plays an active role in macrophage polarization. […] By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with COVID19. […] In favor of BTKi discontinuation, we note a potentially increased risk of secondary infections or impaired humoral immunity. […] We hypothesize that the potential benefit of blunting a hyper-inflammatory response to SARS-CoV-2 through attenuation of M1 polarization outweighs the potential risk of impaired humoral immunity, not to mention the risk of rapid progression of B-cell malignancy following BTKi interruption. […] Based on this, we suggest continuing BTKi in patients with COVID19.
32503877 Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. […] Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. […] Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. […] These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.
32640487 Bruton’s tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID-19 immunopathology. […] Clinical trials with BTK inhibitors in COVID-19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. […] These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID-19. […] Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.
32647324 In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
32736596 Bemcentinib could potentially reduce viral infection and blocks SARS-CoV-2 spike protein; MEDI3506 is a clinic-ready anti-IL-33 monoclonal antibody with the potential to treat respiratory failure caused by COVID; acalabrutinib is a BTK inhibitor which is anti-viral and anti-inflammatory; zilucoplan is a complement C5 inhibitor which may block the severe inflammatory response in COVID-19 and; nebulised heparin has been shown to bind with the spike protein.
32796683 This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs/MAPKs/NF-κB/SYK-BTK signaling pathways.
32948613 Meanwhile, BTK inhibitors, such as acalabrutinib, could prove effective in mitigating severe, hyperinflammatory COVID-19.
33043320 Ibrutinib, a known Burton’s tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation. […] We elected to continue ibrutinib the same day he was intubated, reasoning that BTK inhibition in myeloid immune cells has been shown to reduce or even reverse influenza-mediated acute lung injury and that ITK inhibition in T cells has correlated with reduction in viral replication, and therefore may have an advantage in this setting.
33226337 Bruton’s tyrosine kinase (BTK) is targeted in the treatment of B-cell disorders including leukemias and lymphomas. […] Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site. […] While effective at blocking the catalytic activity of BTK, consequences of drug binding on the global conformation of full-length BTK are unknown. […] Here, we uncover a range of conformational effects in full-length BTK induced by a panel of active site inhibitors, including large-scale shifts in the conformational equilibria of the regulatory domains. […] Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form. […] Future development of BTK inhibitors will need to consider long-range allosteric consequences of inhibitor binding, including the emerging application of these BTK inhibitors in treating COVID-19.
33328281 Recently, Bruton tyrosine kinase (BTK) has emerged as an interesting candidate. […] Elevated levels of BTK activity have been reported in blood monocytes from patients with severe COVID-19, compared with those from healthy volunteers. […] Importantly, various studies confirmed empirically that administration of BTK inhibitors (acalabrutinib and ibrutinib) decreased the duration of mechanical ventilation and mortality rate for hospitalized patients with severe COVID-19. […] Herein, we review the current information regarding the role of BTK in severe acute respiratory syndrome coronavirus 2 infections and the suitability of its inhibitors as drugs to treat COVID-19. […] The use of BTK inhibitors in the management of COVID-19 shows promise in reducing the severity of the immune response to the infection and thus mortality. […] However, BTK inhibition may be contributing in other ways to inhibit the effects of the virus and this will need to be carefully studied.
33441177 Bruton’s tyrosine kinase (BTK) inhibitors, drugs utilized in cancer, are being repurposed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (COVID-19). […] Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2. […] Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is clearly of importance to determine how acalabrutinib, ibrutinib and possibly other BTK inhibitors may provide protection against lung injury.