Design, synthesis, and biological evaluation of pyrrolopyrimidine derivatives as novel Bruton's tyrosine kinase (BTK) inhibitors
Source : https://www.sciencedirect.com/science/article/abs/pii/S022352342200513X?via=ihub
A series of pyrrolopyrimidine-containing BTK inhibitors were synthesized. * 42 demonstrated excellent kinase selectivity and low toxicity. * 42 showed a significant in vivo antitumor activity. Developing Bruton's tyrosine kinase...
Relevance: Developing Bruton's tyrosine kinase (BTK) inhibitors has become a significant focus in recent years because BTK inhibition is an effective approach for the treatment of B-cell malignancies. For covalent BTK inhibitors, low oral bioavailability and low kinase selectivity remain unaddressed issues; thus, more diverse inhibitors with...
Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma - Molecular Medicine
Source : https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00518-0
Background Diffuse large B cell lymphoma (DLBCL) is an aggressive and molecularly heterogeneous non-Hodgkin's lymphoma. The B cell receptor (BCR) signaling pathway in DLBCL emerges as a new drug target....
Conclusions: These data suggest that SHP-1 negatively regulates phosphorylation of Lyn, and targeting SHP-1/p-Lyn using SHP-1 agonist has therapeutic potential for treatment of DLBCL.
The Use of Bruton Tyrosine Kinase Inhibitors in Waldenström's Macroglobulinemia - Clinical Hematology International
Source : https://link.springer.com/article/10.1007/s44228-022-00007-5
The use of Bruton Tyrosine Kinase (BTK) inhibitors in Waldenström's Macroglobulinemia (WM) is evolving. Ibrutinib, a first-generation BTK inhibitor, is currently approved for use in frontline and relapsed/refractory disease. Second-generation...
Conclusion/Relevance: Here, we review the use of BTK inhibitors in WM in front-line and refractory or relapsed settings. We also highlight common adverse events, the emergence of BTK inhibitors resistance, and future directions of their use.
Next-generation Bruton's tyrosine kinase (BTK) inhibitors potentially targeting BTK C481S mutation- Recent developments and Perspectives - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35927919/
Bruton's tyrosine kinase (BTK) plays a vital role in B-cell antigen receptor (BCR) signalling transduction pathway. Controlling BCR signalling by BTK inhibitors is a promising therapeutic approach for the treatment...
Relevance: In this review, we summarized the discovery and development of next-generation BTK inhibitors, specially targeting to BTK C481S mutation and their applications for the treatment of lymphomas and autoimmune diseases.
Enrichment of BTK Leu528Trp mutations in Patients with CLL on Zanubrutinib: Potential for Pirtobrutinib Cross Resistance
Research Article | Piers Blombery, Ella R Thompson, Thomas E Lew, Ing Soo Tiong, Rory Bennett, Chan Y Cheah, Katharine Louise Lewis, Sasanka M Handunnetti, Chloe Pek Sang Tang, Andrew...
Relevance: We describe 2 patients with BTK Leu528Trp mutations who showed clinical cross-resistance and progressive enrichment of the BTK Leu528Trp mutation over time when treated with the non-covalent BTK inhibitor pirtobrutinib. Both patients subsequently responded to venetoclax based treatment. In summary we have identified an enrichment of...