scholarly journals Discovery of new BTK inhibitors with B cell suppression activity bearing a 4,6-substituted thieno[3,2-d]pyrimidine scaffold

RSC Advances ◽  
2017 ◽  
Vol 7 (42) ◽  
pp. 26060-26069 ◽  
Author(s):  
Qiumeng Zhang ◽  
Luyao Zhang ◽  
Jie Yu ◽  
Heng Li ◽  
Shijun He ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
B Cell ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Bruton’S Tyrosine Kinase ◽  
Immunosuppressive Activity ◽  
Bruton's Tyrosine Kinase ◽  
Low Toxicity ◽  
Cell Suppression ◽  
Btk Inhibitors

Seventeen compounds with 4,6-substituted thieno[3,2-d]pyrimidine scaffold were prepared as new Bruton's tyrosine kinase inhibitors. Compound 8 exhibits anti-BTK activity, immunosuppressive activity, enzymatic selectivity and low toxicity.

Resistance to Bruton's Tyrosine Kinase Inhibitors: The Achilles Heel of Their Success Story in Lymphoid Malignancies

Blood ◽  
2021 ◽  
Author(s):  
Deborah M. Stephens ◽  
John C Byrd
Keyword(s):  
Tyrosine Kinase ◽  
B Cell ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
Treatment Modalities ◽  
Bruton’S Tyrosine Kinase ◽  
B Cell Malignancies ◽  
Bruton's Tyrosine Kinase ◽  
Resistant Disease

Bruton's tyrosine kinase inhibitors (BTKi) have significantly changed the treatment landscape for patients with B-cell malignancies including chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia (WM), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Unfortunately, patients with BTKi resistant disease have shortened survival. Clinical and molecular risk factors, such as number of prior therapies and presence of TP53 mutations, can be used to predict patients at the highest risk of developing BTKi resistance. Many mechanisms of BTKi resistance have been reported with mutations in BTK and phospholipase C g 2 supported with the most data. The introduction of venetoclax has lengthened the survival of patients with BTKi resistant disease. Ongoing clinical trials with promising treatment modalities such as next-generation BTKi and chimeric antigen receptor T-cell therapy have reported promising efficacy in patients with BTKi resistant disease. Continued research focusing on resistance mechanisms and methods of how to circumvent resistance is needed to further prolong the survival of patients with BTKi resistant B-cell malignancies.

Development of Bruton’s Tyrosine Kinase Inhibitors for Rheumatoid Arthritis

2019 ◽  
Vol 25 (42) ◽  
pp. 5847-5859 ◽  
Author(s):  
Jiahui Lv ◽  
Jingde Wu ◽  
Feng He ◽  
Ying Qu ◽  
Qiuqiong Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Kinase Inhibitors ◽  
Hot Spot ◽  
Work Force ◽  
Activation Process ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Btk Inhibitors

Rheumatoid Arthritis (RA) is a chronic autoimmune disease and becomes one of the major causes of disability and work force loss. The presence of abnormal B cell and autoantibodies produced by most RA patients, primarily ACPA and RF, indicate that the function of B cell was involved in the development of RA disease. Accordingly, the drug targeting B cell has become a hot spot in the treatment of RA. Studies have shown that Bruton's tyrosine kinase (BTK) is involved in the regulation of B cell proliferation and activation process. Some small molecule BTK inhibitors have shown excellent inhibition in biological activity analysis and animal models. Therefore, this review will briefly introduce BTK and its role in cell signaling and overview recent progress of BTK inhibitors for RA treatment.

scholarly journals Observations on the use of Bruton’s tyrosine kinase inhibitors in SAR-CoV-2 and cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Brooke Benner ◽  
William E. Carson
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Innate Immune ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Process Understanding ◽  
Btk Inhibitors ◽  
Severe Lung Disease ◽  
Pro Inflammatory Cytokines ◽  
Severe Lung

AbstractBruton’s tyrosine kinase (BTK) inhibitors, drugs utilized in cancer, are being repurposed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (COVID-19). Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2. The high levels of pro-inflammatory cytokines found in the circulation of COVID-19 patients with severe lung disease suggest the involvement of the innate immune system in this process. Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is clearly of importance to determine how acalabrutinib, ibrutinib and possibly other BTK inhibitors may provide protection against lung injury.

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