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

Gu, Danling; Tang, Hui; Wu, Jia‐Zhu; Li, Jianyong; Miao, Yi

doi:10.1186/s13045-021-01049-7

Cited by 69 publications

(69 citation statements)

References 92 publications

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“…Reversible inhibitors do not bind to cysteine-481 and are good alternatives for persons with B-cell malignancies who do not respond to irreversible inhibitors due to BTK cysteine-481 mutations [71]. Reversible inhibitors non-covalently bind to different BTK-specific pockets with hydrogen bonds, ionic bonds, or hydrophobic forces [68].…”

Section: Btk Inhibitorsmentioning

confidence: 99%

Bruton’s Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy

García‐Merino

2021

Cells

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B cells play a central role in the pathogenesis of multiple sclerosis (MS), as demonstrated through the success of various B cell-depleting monoclonal antibodies. Bruton’s tyrosine kinase (BTK) is a critical molecule in intracellular signaling from the receptor of B cells and receptors expressed in the cells of the innate immune system. BTK inhibitors may be a non-cell-depleting alternative to B cell modulation. In this review, the structure, signaling, and roles of BTK are reviewed among the different inhibitors assayed in animal models of MS and clinical trials.

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Section: Btk Inhibitorsmentioning

confidence: 99%

Bruton’s Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy

García‐Merino

2021

Cells

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“…Treatment of patients with CLL has come a long way and medicine never stops advancing. There are emerging therapies and novel combinations on the horizon, including second-generation and noncovalent BTK inhibitors permitting optimization of this important drug class [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Frontline Treatment of the Young, Fit Patient with CLL: A Canadian Perspective

2021

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From a Canadian perspective, there has been a limited discussion on the frontline management of young, fit patients with chronic lymphocytic leukemia (CLL). The prevalence of this population ranges between 2 and 22 per 100,000 persons in Canada and varies by region. Until recently, fixed-duration fludarabine-based chemoimmunotherapy (CIT) was the primary treatment option in Canada for this patient population. The ECOG1912 trial has since demonstrated that ibrutinib and rituximab therapy are as effective as fludarabine-cyclophosphamide-rituximab (FCR) in this population. The ALLIANCE trial showed that rituximab added no incremental benefit to ibrutinib. Canadian payors and physicians adopted ibrutinib monotherapy as the CLL standard of care, even in the young, fit population, although frontline ibrutinib therapy is often reimbursed by provincial public drug plans only in patients with high-risk disease or those who are unfit to receive fludarabine. Young, fit patients with CLL and their physicians may now choose between continuous ibrutinib monotherapy and fixed-duration CIT with FCR. Factors affecting this choice include patient preference and the short- and long-term toxicity profiles of both regimens, and a risk-based algorithm is provided. As new continuous-therapy options enter the market, all treatment choices present benefits and risks that must be communicated to the patient.

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“…Unlike ibrutinib and second-generation BTK inhibitors, next-generation BTK inhibitors such as vecabrutinib (SNS-062), pirtobrutinib (LOXO-305), and MK1026 (ARQ-351), are reversible inhibitors which do not interact with the BTK C481 site and can therefore conceivably overcome resistance associated with mutations at this residue. Some of these agents are currently undergoing clinical trials in patients with B-cell lymphoproliferative disorders, including WM, and preliminary results are encouraging ( 79 ).…”

Section: Mechanisms Of Drug Resistance In Lpl/wmmentioning

confidence: 99%

Determinants of Drug Resistance in B-Cell Non-Hodgkin Lymphomas: The Case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia

et al. 2022

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Lymphoplasmacytic lymphoma (LPL) is a rare subtype of B cell-derived non-Hodgkin lymphoma characterized by the abnormal growth of transformed clonal lymphoplasmacytes and plasma cells. This tumor almost always displays the capability of secreting large amounts of monoclonal immunoglobulins (Ig) of the M class (Waldenström Macroglobulinemia, WM). The clinical manifestations of WM/LPL may range from an asymptomatic condition to a lymphoma-type disease or may be dominated by IgM paraprotein-related symptoms. Despite the substantial progresses achieved over the last years in the therapy of LPL/WM, this lymphoma is still almost invariably incurable and exhibits a propensity towards development of refractoriness to therapy. Patients who have progressive disease are often of difficult clinical management and novel effective treatments are eagerly awaited. In this review, we will describe the essential clinical and pathobiological features of LPL/WM. We will also analyze some key aspects about the current knowledge on the mechanisms of drug resistance in this disease, by concisely focusing on conventional drugs, monoclonal antibodies and novel agents, chiefly Bruton’s Tyrosine Kinase (BTK) inhibitors. The implications of molecular lesions as predictors of response or as a warning for the development of therapy resistance will be highlighted.

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

Cited by 69 publications

References 92 publications

Bruton’s Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy

Bruton’s Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy

Frontline Treatment of the Young, Fit Patient with CLL: A Canadian Perspective

Determinants of Drug Resistance in B-Cell Non-Hodgkin Lymphomas: The Case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia

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