Bruton’s Tyrosine Kinase Inhibitors: Approaches to Potent and Selective Inhibition, Preclinical and Clinical Evaluation for Inflammatory Diseases and B Cell Malignancies

2012 ◽  
Vol 55 (10) ◽  
pp. 4539-4550 ◽  
Author(s):  
Yan Lou ◽  
Timothy D. Owens ◽  
Andreas Kuglstatter ◽  
Rama K. Kondru ◽  
David M. Goldstein
Keyword(s):  
Tyrosine Kinase ◽  
B Cell ◽  
Tyrosine Kinase Inhibitors ◽  
Clinical Evaluation ◽  
Kinase Inhibitors ◽  
Inflammatory Diseases ◽  
Selective Inhibition ◽  
Bruton’S Tyrosine Kinase ◽  
B Cell Malignancies ◽  
Bruton's Tyrosine Kinase

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.

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.

scholarly journals Novel Indications for Bruton’s Tyrosine Kinase Inhibitors, beyond Hematological Malignancies

2018 ◽  
Vol 7 (4) ◽  
pp. 62 ◽  
Author(s):  
Robert Campbell ◽  
Geoffrey Chong ◽  
Eliza Hawkes
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Hematological Malignancies ◽  
Kinase Inhibitors ◽  
Cell Receptor ◽  
Bruton’S Tyrosine Kinase ◽  
B Cell Malignancies ◽  
Bruton's Tyrosine Kinase ◽  
Novel Target

Bruton’s tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies. In addition to the expansion of the role of BTKi monotherapy, combination therapy strategies utilizing ibrutinib with established regimens and combination with modern immunotherapy compounds are being explored.

Sign in / Sign up

Export Citation Format

Share Document