1995年5月1日 · Using a random mutagenesis scheme, we isolated a gain-of-function mutant called BTK* whose expression drives growth of NIH 3T3 cells In soft agar. BTK* results from a single point mutation In the pleckstrin homology (PH) domain, where a …

2019年10月15日 · We compared functional effects of the JAK1/2 inhibitors momelotinib and ruxolitinib, the BTK inhibitors ibrutinib and tirabrutinib, and PI3Kδ inhibitor idelalisib on malignant CLL cells but also on healthy human T, B, and NK lymphocytes. We found several interesting differences among the inhibitors, apart from expected and well-known effects.

1999年4月16日 · In NIH 3T3 cells coexpressing BtkPH-GFP and the epidermal growth factor receptor, activation of epidermal growth factor or endogenous platelet-derived growth factor receptors caused a rapid (<3 min) translocation of the cytosolic fluorescence to ruffle-like membrane structures.

2022年8月8日 · Recent clinical trials have shown promising results for the next-generation Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib in the treatment of multiple sclerosis (MS). BTK has a central role in signaling pathways that govern the development of B cells. Whether and how BTK activity shapes B cells as key drivers of MS is currently unclear.

2024年4月23日 · We gene-edited mice substituting tyrosine 223 for nonphosphorylatable phenylalanine and found no difference from wild-type animals. Bruton’s tyrosine kinase (BTK) is an enzyme needed for B-cell survival, and its inhibitors have become potent targeted medicines for the treatment of B-cell malignancies.

Wild-type Btk and Btk* were expressed in NIH 3T3 cells by retroviral infection. Following in vivo 32P-orthophos-phate labeling, Btk proteins were immunoprecipitated from cell extracts and analyzed by two-dimensional tryptic phosphopeptide mapping (Boyle et al., 1991).

2001年10月15日 · We provide direct evidence that PKCβ acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCβ results in a dramatic increase in B‐cell receptor (BCR)‐mediated Ca 2+ signaling. We identified a highly conserved PKCβ serine phosphorylation site in a short linker within the Tec homology domain of Btk.

2024年11月1日 · Bruton's Tyrosine Kinase (BTK) played a key role in the B cell antigen receptor (BCR) signaling pathway, and was considered a hotspot in the treatment of B cell malignant tumors and B cell immune diseases. There were 5 covalent irreversible inhibitors launched currently on the market, but C481S muta …

2019年11月13日 · We have identified multiple CTMs that catalyze BTK degradation in multiple B cell lines; the concentration of one of such CTM, NRX0492, required to degrade 50% BTK (DC 50) was < 1 nM after 4 hours. BTK CTMs impair viability in the BTK-dependent ABC-DLBCL cell line, TMD8 (EC 50: < 10 nM after 72 hours).

2018年6月6日 · In this study, for the first time, we report the development of BTK-targeting degraders using the PROTAC strategy. These PROTACs could efficiently degrade ibrutinib-sensitive BTK-WT (wild type).