Recent research of BTK inhibitors: Methods of structural design, pharmacological activities, manmade derivatives and structure–activity relationship

Wang, Lin; Zhang, Zhengjie; Yu, Dongke; Yang, Liuqing; Li, Ling; He, Yuehui; Shi, Jianyou

doi:10.1016/j.bioorg.2023.106577

Cited by 3 publications

(2 citation statements)

References 136 publications

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“…Pirtobrutinib is a potent, non-covalent (reversible), highly selective inhibitor of both BTK and C481 mutant BTK. Pirtobrutinib functions by binding to BTK via an extensive network of interactions with water molecules in the ATP binding region, rather than directly interacting with the C481 site, demonstrating potential to overcome resistance to covalent BTK inhibitors ( 58 , 59 ). On January 27, 2023, the FDA expedited approval of pirtobrutinib for the treatment of R/R MCL patients who have received at least two lines of systemic therapy, including BTK inhibitors ( 60 ).…”

Section: Emerging Therapiesmentioning

confidence: 99%

Advances in the treatment of relapsed/refractory marginal zone lymphoma

Wang,

Wan,

Zhang

et al. 2024

Front. Oncol.

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Marginal zone lymphoma (MZL) is the second most common subtype of inert B-cell non-Hodgkin’s lymphoma, accounting for 5–15% of non-Hodgkin’s lymphoma cases. Patients with MZL have a long survival period, with a median survival of >10 years, and patients treated with a combination of anti-CD20 monoclonal antibody can achieve an overall effective rate of 81%. However, 20% of patients with MZL show relapse or experience disease progression within 2 years, with a median survival of only 3–5 years. Currently, the treatment options for patients with relapsed/refractory (R/R) MZL are limited, underscoring the pressing need for novel therapeutic drugs. The advent of novel anti-CD20 monoclonal antibodies, small molecule kinase inhibitors, immunomodulators, and other therapeutic strategies has ushered in a new era in the treatment of R/R MZL. Our objective is to summarize the existing treatment strategies, including immunotherapy and the emergent targeted therapies, and to evaluate their effectiveness and safety in the management of R/R MZL. By doing so, we aim to provide a clear understanding of the therapeutic landscape for R/R MZL, and to guide future research directions toward improving the prognosis and quality of life for patients afflicted with this challenging disease.

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Section: Emerging Therapiesmentioning

confidence: 99%

Advances in the treatment of relapsed/refractory marginal zone lymphoma

Wang,

Wan,

Zhang

et al. 2024

Front. Oncol.

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“…Bleeding events related to BTKis are due to the off-target inhibition of Tec kinase, which disrupts platelet activation pathways and suppresses Glycoprotein VI (GPVI) signaling [ 82 , 83 , 84 , 85 ]. The concurrent administration of antiplatelet drugs, such as aspirin or P2Y12 inhibitors, with BTKis further increases the risk of bleeding.…”

Section: Class Effect Profile and Adverse Events Management: Btk Inhi...mentioning

confidence: 99%

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents

Galitzia,

Maccaferri,

Mauro

et al. 2024

Cancers

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The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton’s Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy.

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