Summary Ibrutinib is highly active in Waldenstrm macroglobulinaemia (WM) patients, but disease progression can occur due to acquired mutations in BTK, the target of ibrutinib, or PLCG2, the protein downstream of BTK. However, not all resistant patients harbour these alterations. We have performed...
catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant A Hamasy1,4, Q Wang1,4, KEM Blomberg1, DK Mohammad1, L Yu2, M Vihinen3, A Berglöf1 and CIE Smith1 Irreversible Bruton tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib have demonstrated ...
A new potent BTKC481SPROTAC with a much smaller molecular weight, improved solubility and shorter synthetic route was developed for ibrutinib-resistant malignant lymphoma. Notably, the newly developed degrader demonstrates better BTK degrading activity and lower IC50value in ibrutinib-resistant cell line...
Additionally, activated B-cell-like (ABC)-DLBCL patients achieved remission after treatment with ibrutinib [8]. Unfortunately, drug-resistant tumor cells have been isolated from MCL patients during treatment with ibrutinib and the relapse-specific C481S missense BTK mutation contributes to this ...
The Bruton Kinase (BTK) inhibitor, ibrutinib, pioneered a paradigm shift in the treatment of chronic lymphocytic leukemia (CLL), especially in high-risk cytogenetic groups. Despite its transformative efficacy, it can be associated with a high discontinuation rate, particularly in the community setting...
ibrutinib‐resistantBackground: Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 ...
However, the bottleneck of ibrutinib resistance has caused widespread concerns, necessitating the exploration of novel targets. MethodsSingle-cell RNA sequencing (scRNA-seq) was used to characterize the heterogeneity of ibrutinib-sensitive (IBS) and -resistant (IBR) CLL patients and single-cell stem...
Disclosed are methods of treating an ibrutinib-resistant disease in a mammal with a compound of Formula (I): wherein R is described herein. In certain embodiments, a compound of Formula (I) inhibits the activity of a variant Btk, providing a method of treating ibrutinib-resistant diseases, ...
Disclosed are methods of treating an ibrutinib-resistant disease in a mammal with a compound of Formula (I): wherein R is described herein. In certain embodiments, a compound of Formula (I) inhibits the activity of a variant Btk, providing a method of treating ibrutinib-resistant diseases, ...
Early reappearance of intraclonal proliferative subpopulations in ibrutinib-resistant chronic lymphocytic leukemiaThe Bruton's tyrosine kinase (BTK) inhibitor ibrutinib represents an effective strategy for treatment of chronic lymphocytic leukemia (CLL), nevertheless about 30% of patients eventually undergo ...