Bruton tyrosine kinase inhibitors for multiple sclerosis

Nature Reviews Neurology, Год журнала: 2023, Номер 19(5), С. 289 - 304

Опубликована: Апрель 13, 2023

Язык: Английский

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BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 1, 2022

Bruton's tyrosine kinase (BTK) is an essential component of multiple signaling pathways that regulate B cell and myeloid proliferation, survival, functions, making it a promising therapeutic target for various malignancies inflammatory diseases. Five small molecule inhibitors have shown remarkable efficacy been approved to treat different types hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, orelabrutinib. The first-in-class agent, has created new era chemotherapy-free treatment malignancies. Ibrutinib so popular became the fourth top-selling cancer drug worldwide in 2021. To reduce off-target effects overcome acquired resistance significant efforts made developing highly selective second- third-generation BTK combination approaches. Over past few years, also repurposed Promising data obtained from preclinical early-phase clinical studies. In this review, we summarized current progress applying disorders, highlighting available results

Язык: Английский

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Regulatory Mechanism of M1/M2 Macrophage Polarization in the Development of Autoimmune Diseases

Mediators of Inflammation, Год журнала: 2023, Номер 2023, С. 1 - 20

Опубликована: Июнь 8, 2023

Macrophages are innate immune cells in the organism and can be found almost tissues organs. They highly plastic heterogeneous participate response, thereby playing a crucial role maintaining homeostasis of body. It is well known that undifferentiated macrophages polarize into classically activated (M1 macrophages) alternatively (M2 under different microenvironmental conditions. The directions macrophage polarization regulated by series factors, including interferon, lipopolysaccharide, interleukin, noncoding RNAs. To elucidate various autoimmune diseases, we searched literature on with PubMed database. Search terms as follows: macrophages, polarization, signaling pathways, RNA, inflammation, systemic lupus erythematosus, rheumatoid arthritis, nephritis, Sjogren’s syndrome, Guillain-Barré multiple sclerosis. In present study, summarize common diseases. addition, also features recent advances particular focus immunotherapeutic potential diseases potentially effective therapeutic targets.

Язык: Английский

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Protein kinases: drug targets for immunological disorders

Nature reviews. Immunology, Год журнала: 2023, Номер 23(12), С. 787 - 806

Опубликована: Май 15, 2023

Язык: Английский

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Bruton’s Tyrosine Kinase Inhibitors (BTKIs): Review of Preclinical Studies and Evaluation of Clinical Trials

Molecules, Год журнала: 2023, Номер 28(5), С. 2400 - 2400

Опубликована: Март 6, 2023

In the last few decades, there has been a growing interest in Bruton’s tyrosine kinase (BTK) and compounds that target it. BTK is downstream mediator of B-cell receptor (BCR) signaling pathway affects proliferation differentiation. Evidence demonstrating expression on majority hematological cells led to hypothesis inhibitors (BTKIs) such as ibrutinib can be an effective treatment for leukemias lymphomas. However, body experimental clinical data demonstrated significance BTK, not just malignancies, but also solid tumors, breast, ovarian, colorectal, prostate cancers. addition, enhanced activity correlated with autoimmune disease. This gave rise beneficial therapy rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Sjögren’s syndrome (SS), allergies, asthma. this review article, we summarize most recent findings regarding well advanced have developed date their applications mainly cancer chronic inflammatory disease patients.

Язык: Английский

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Bruton’s Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(10), С. 2807 - 2807

Опубликована: Май 16, 2022

The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the management patients with B-cell lymphoid malignancies. BTK is an important molecule that interconnects antigen receptor (BCR) signaling. (BTKis) are classified into three categories, namely covalent irreversible inhibitors, reversible and non-covalent inhibitors. Ibrutinib first covalent, inhibitor approved in 2013 as a breakthrough therapy for chronic lymphocytic leukemia patients. Subsequently, two other irreversible, second-generation BTKis, acalabrutinib zanubrutinib, have been developed malignancies to reduce ibrutinib-mediated adverse effects. More recently, BTKis under development immune-mediated diseases, including autoimmune hemolytic anemia, immune thrombocytopenia, multiple sclerosis, pemphigus vulgaris, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, spontaneous urticaria, among others. This review article summarizes preclinical clinical evidence supporting role various autoimmune, allergic, inflammatory conditions.

Язык: Английский

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Targeting B cells and plasma cells in autoimmune diseases: From established treatments to novel therapeutic approaches

European Journal of Immunology, Год журнала: 2022, Номер 53(1)

Опубликована: Окт. 31, 2022

Autoimmune diseases are characterized by the recognition of self-antigens immune system, which leads to inflammation and tissue damage. B cells directly indirectly involved in pathophysiology autoimmunity, both via antigen-presentation T production proinflammatory cytokines and/or autoantibodies. Consequently, lineage have been identified as therapeutic targets autoimmune diseases. cell depleting strategies proven beneficial treatment rheumatoid arthritis (RA), systemic lupus erythematous (SLE), ANCA-associated vasculitis (AAV), multiple sclerosis (MS), a wide range other immune-mediated inflammatory (IMIDs). However, not all patients respond or may reach (drug-free) remission. Moreover, therapies do always target subsets, such short-lived long-lived plasma cells. These play an active role autoimmunity certain their depletion would be achieve disease In current review article, we provide overview novel diseases, with focus on rheumatic Both advanced that recently become available more experimental treatments clinic near future discussed.

Язык: Английский

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Future landscape for the management of membranous nephropathy

Clinical Kidney Journal, Год журнала: 2023, Номер 16(8), С. 1228 - 1238

Опубликована: Март 8, 2023

Among all glomerular diseases, membranous nephropathy (MN) is perhaps the one in which major progress has been made recent decades, both understanding of pathogenesis and treatment. Despite overall significant response rates to these therapies-particularly rituximab cyclical regimen based on corticosteroids cyclophosphamide-cumulative experience over years shown, however, that 20%-30% cases may confront resistant disease. Thus, unmet challenges treatment forms MN require newer approaches. Several emerging new agents-developed primarily for hematological malignancies or rheumatoid diseases-are currently being evaluated MN. Herein we conducted a narrative review future therapeutic strategies different novel therapies, anti-CD20 agents (e.g. obinutuzumab), anti-CD38 daratumumab, felzartamab), immunoadsorption anti-complement therapies iptacopan) have gained special attention. In addition, several technologies innovations developed cancer chimeric antigen receptor T-cell therapy, sweeping antibodies) seem particularly promising. summary, landscape seems encouraging will definitely move management this disease towards more precision-based approach.

Язык: Английский

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Sequential immunotherapy: towards cures for autoimmunity

Nature Reviews Drug Discovery, Год журнала: 2024, Номер 23(7), С. 501 - 524

Опубликована: Июнь 5, 2024

Язык: Английский

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Epigenetic regulation of B cells and its role in autoimmune pathogenesis

Cellular and Molecular Immunology, Год журнала: 2022, Номер 19(11), С. 1215 - 1234

Опубликована: Окт. 12, 2022

Abstract B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation patients various disorders, progress epigenetic research has revealed new mechanisms leading to hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate responses, their dysregulation can contribute Patients diseases show alterations that lead initiation perpetuation inflammation. Moreover, clinical animal model promising potential therapies for patients. In this review, we present an up-to-date overview focus on roles regulating functional subsets. Furthermore, discuss highlight its contribution development Based preclinical evidence, novel biomarkers disorders.

Язык: Английский

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