Noncovalent inhibition of C481S Bruton tyrosine kinase by GDC-0853: a new treatment strategy for ibrutinib-resistant CLL
نویسندگان
چکیده
منابع مشابه
Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms.
The Bruton non-receptor protein-tyrosine kinase (BTK), a deficiency of which leads to X-linked agammaglobulinemia, plays a central role in B cell antigen receptor signaling. Owing to the exclusivity of this enzyme in B cells, the acronym could represent B cell tyrosine kinase. BTK is activated by the Lyn and SYK protein kinases following activation of the B cell receptor. BTK in turn catalyzes ...
متن کاملIbrutinib: A New Frontier in the Treatment of Chronic Lymphocytic Leukemia by Bruton’s Tyrosine Kinase Inhibition
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of nonfunctional mature B cells in blood, bone marrow and lymphoid tissues. In the last decade, our understanding of CLL and consequently our diagnostic and therapeutic approaches have changed dramatically. Conventional fludarabine based chemotherapy has led to improved disease response and longer survival in young ...
متن کاملPanniculitis in Patients Undergoing Treatment With the Bruton Tyrosine Kinase Inhibitor Ibrutinib for Lymphoid Leukemias.
Panniculitis in Patients Undergoing Treatment With the Bruton Tyrosine Kinase Inhibitor Ibrutinib for Lymphoid Leukemias Ibrutinib is an oral inhibitor of Bruton tyrosine kinase (BTK) withmarked activity in several B-cell malignant neoplasms.1 Commonly reported adverse events include diarrhea, infection, fatigue, arthralgias, pyrexia, hypertension, and neutropenia.2 Grade 1 and 2 rashes have be...
متن کاملFirst-in-human phase 1 study of the BTK inhibitor GDC-0853 in relapsed or refractory B-cell NHL and CLL
GDC-0853 is a selective, reversible, and non-covalent inhibitor of Bruton's tyrosine kinase (BTK) that does not require interaction with the Cys481 residue for activity. In this first-in-human phase 1 study we evaluated safety, tolerability, pharmacokinetics, and activity of GDC-0853 in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Twenty...
متن کاملBTK (Bruton agammaglobulinemia tyrosine kinase)
The BTK protein is a 77 kDa protein of 659 amino acids. Translation of the BTK transcript starts at the ATG site that is located in exon 2 and ends in exon 19. The BTK protein is composed of an N-terminal Pleckstrin homology (PH) domain followed three protein interacting domains: Tec homology (TH) region, Src homology 3 (SH3) domain and SH2 domain. A tyrosine-kinase catalytic domain is located ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Blood
سال: 2018
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2017-10-809020