Zanubrutinib for the treatment of Waldenström Macroglobulinemia

Lim, Kenneth; Tam, Constantine S.

doi:10.1080/17474086.2020.1851184

Cited by 4 publications

(3 citation statements)

References 48 publications

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“…Zanubrutinib (ZB), a second-generation BTK inhibitor, is currently used in the treatment of capsid cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [ 19 ]. ZB is highly selective for BTK, a property that is intended to increase drug potency and reduce off-target effects [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

Zhu

Liu

et al. 2023

Molecules

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(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which have now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous research has demonstrated that Bruton’s tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation; (2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish a cardiac fibrosis animal model; (3) Results: In vivo: Results showed that the BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage pro-inflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by the BTK, STAT3, NF-κB, and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.

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Section: Introductionmentioning

confidence: 99%

Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

Zhu

Liu

et al. 2023

Molecules

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“…In 2020, a thorough review describing research on zanubrutinib to treat WM was published [ 36 ]. There have been many advances in WM treatment since then.…”

Section: Introduction: Background On Waldenström Macroglobulinemiamentioning

confidence: 99%

Coming of Age for BTK Inhibitor Therapy: A Review of Zanubrutinib in Waldenström Macroglobulinemia

Muñoz

Paludo

Sarosiek

et al. 2022

Cells

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Waldenström macroglobulinemia (WM) is a rare form of non-Hodgkin B-cell lymphoma with a variable clinical presentation that can impact a patient’s quality of life by causing anemia, peripheral neuropathy, serum hyperviscosity, extramedullary disease, and other symptoms. There are several safe and effective treatment regimens for patients with WM, and the choice of therapy should be made in a personalized fashion considering the patient’s symptoms, comorbidities, and genomic profile. Bruton tyrosine kinase (BTK) inhibitors are a new option to treat patients with WM. Zanubrutinib is a next-generation covalent BTK inhibitor designed to have fewer off-target effects than previous BTK inhibitors. This review summarizes the pharmacokinetic and pharmacodynamic properties of zanubrutinib as well as safety and efficacy findings. Then, it explores the health economic and outcomes research associated with the costs of treating patients with WM and the reasons why zanubrutinib may be a more cost-effective treatment option compared with ibrutinib, a first-generation BTK inhibitor. Future directions for the treatment of WM focus on the use of zanubrutinib in combination therapy. Combinations based on effective ibrutinib or acalabrutinib treatments may be effectively applied with zanubrutinib given the similar mechanism of action for these BTK inhibitors. Combination therapies could also help prevent the development of disease resistance, minimize toxicity, and support treatment regimens of finite duration.

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“…ZB is a second-generation BTK inhibitor with increased specificity to BTK. The role of this greater selectivity toward BTK aims to increase potency of the drug and reduce off-target effects [15]. ZB is clinically used for the treatment of Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [16].…”

Section: Introductionmentioning

confidence: 99%

Zanubrutinib Attenuated Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

Wei

Gu³

et al. 2021

Preprint

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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial lung disease with high mortality and limited treatment. So far, the only drugs approved for the treatment of IPF are Nintedanib and Pirfenidone. Zanubrutinib, a BTK small molecule inhibitor, is approved for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In this study, we explored the potential effect and mechanisms of zanubrutinib on pulmonary fibrosis in vivo and in vitro. Methods: In the in vivo experiments, different doses of zanubrutinib were administered in a mouse model of bleomycin-induced pulmonary fibrosis, and pathological manifestations and lung function indexes were evaluated. The in vitro experiments were used a TGF-β1-treated fibroblast model to evaluate the effect of zanubrutinib on the activation and autophagy phenotype of fibroblasts and explored the underlying signaling pathways mechanism. Results: In vivo experiments proved that zanubrutinib effectively attenuated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro mechanism study indicated that zanubrutinib could suppress collagen deposition, myofibroblast activation by inhibiting the TGF-β1/Smad pathway and induce autophagy through the TGF-β1/mTOR pathway. Conclusions: Zanubrutinib could alleviate bleomycin- induced lung fibrosis in mice by inhibiting the TGF-β1 signaling pathway.

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Zanubrutinib for the treatment of Waldenström Macroglobulinemia

Cited by 4 publications

References 48 publications

Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

Coming of Age for BTK Inhibitor Therapy: A Review of Zanubrutinib in Waldenström Macroglobulinemia

Zanubrutinib Attenuated Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

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