Bruton’s Tyrosine Kinase Inhibition for the Treatment of Rheumatoid Arthritis

Arneson, Laura; Carroll, Kristen; Ruderman, Eric

doi:10.2147/itt.s288550

Cited by 24 publications

(22 citation statements)

References 39 publications

(99 reference statements)

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“…Bruton's tyrosine kinase (BTK), a member of the Tec family of nonreceptor tyrosine kinases, is a cytoplasmic kinase expressed in B cells and myeloid cells [122]. BTK inhibitors are a new class of drugs that inhibit B cell receptor activation, FC-γ receptor signaling, and osteoclast proliferation [123]. Therefore, BTK inhibitors are promising new drugs with potential efficacy in B cell malignancies.…”

Section: Therapeutic Approaches Under Evaluation In Humansmentioning

confidence: 99%

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Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

Jang

Kwon

Lee

2022

IJMS

194

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Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

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Section: Therapeutic Approaches Under Evaluation In Humansmentioning

confidence: 99%

“…Currently, BTK inhibitors are being investigated to treat a variety of autoimmune diseases, including RA. While the results of BTK inhibitors in animal models of RA are good, the results of subsequent human clinical trials have been somewhat ambiguous [123,125].…”

Section: Therapeutic Approaches Under Evaluation In Humansmentioning

confidence: 99%

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

Jang

Kwon

Lee

2022

IJMS

194

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“…The disease is characterized by B-cell dysregulation via BCR signaling, and dysregulation of T cells, leading to the production of autoantibodies and inflammatory cytokines involved in the development and progression of RA. This may indicate that BTKis can be useful drugs in the treatment of RA [ 104 ].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

“…They also achieved sufficient receptor occupancy with satisfactory pharmacokinetic (PK) and pharmacodynamic (PD) endpoints and were found to be effective in animal models [ 20 , 28 , 29 , 38 , 106 , 107 ]. More recently, irreversible and reversible BTK inhibitors, including acalabrutinib, spebrutinib, evobrutinib, tirabrutinib subrutinib, branebrutinib, poseltinib, TAS5315, and fenebrutinib, are undergoing phase 2 clinical trials ( Table 1 and Table 2 ) [ 36 , 104 , 107 , 108 , 109 ].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

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

Robak

2022

JCM

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

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“…From a myeloid tissue perspective, BTK plays a role in mast cell activation via the high-affinity IgE receptor (14). Given these roles, BTK inhibitors are being evaluated for the treatment of B-cell malignancies (15), as well as for inflammatory and autoimmune disorders (16), including RA (17) and MS (18).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Radiopharmaceuticals via “In-Loop” 11C-Carbonylation as Exemplified by the Radiolabeling of Inhibitors of Bruton's Tyrosine Kinase

et al. 2022

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Positron emission tomography (PET) is an important non-invasive tool to help guide the drug discovery and development process. Positron-emitting–radiolabeled drug candidates represent an important tool for drug hunters to gain insight into a drug's biodistribution and target engagement of exploratory biologic targets of interest. Recently, there have been several drug candidates that incorporate an acryloyl functional group due to their ability to form a covalent bond within the biological target of interest through Michael addition. Methods to incorporate a carbon-11 radionuclide into acrylamide derivatives remain challenging given the reactive nature of this moiety. Herein, we report the improved radiosynthesis of carbon-11–containing acrylamide drug candidates, [11C]ibrutinib, [11C]tolebrutinib, and [11C]evobrutinib, using [11C]CO and a novel “in-loop” 11C-carbonylation reaction. [11C]Ibrutinib, [11C]tolebrutinib, and [11C]evobrutinib were reliably synthesized, generating 2.2-7.1 GBq of these radiopharmaceuticals in radiochemical yields ranging from 3.3 to 12.8% (non-decay corrected; relative to starting [11C]CO2) and molar activities of 281-500 GBq/μmol (7.5-13.5 Ci/μmol), respectively. This study highlights an improved method for incorporating carbon-11 into acrylamide drug candidates using [11C]CO within an HPLC loop suitable for clinical translation using simple modifications of standard automated synthesis modules used for cGMP manufacture of PET radioligands.

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Bruton’s Tyrosine Kinase Inhibition for the Treatment of Rheumatoid Arthritis

Cited by 24 publications

References 39 publications

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

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

Synthesis of Radiopharmaceuticals via “In-Loop” 11C-Carbonylation as Exemplified by the Radiolabeling of Inhibitors of Bruton's Tyrosine Kinase

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