Beyond ibrutinib: novel BTK inhibitors for the treatment of chronic lymphocytic leukemia - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35993294/
For the treatment of CLL, several effective therapeutic strategies to target BTK are or will soon be available: these drugs present different safety profiles, thus making it possible to tailor...
Summary: For the treatment of CLL, several effective therapeutic strategies to target BTK are or will soon be available: these drugs present different safety profiles, thus making it possible to tailor the treatment choice according to patient's characteristics. Importantly, noncovalent BTKi will provide a therapeutic chance also for those...
Exploring the Role of Chemical Reactions in the Selectivity of Tyrosine Kinase Inhibitors - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/36044733/
A variety of diseases are associated with tyrosine kinase enzymes that activate many proteins via signal transduction cascades. The similar ATP-binding pockets of these tyrosine kinases make it extremely difficult...
Conclusion/Relevance: Our study involves a new approach of simulating directly the IC50 and inactivation efficiency keff, instead of using the standard formulas. This new strategy is particularly important in studies of covalent inhibitors with a very exothermic bonding step. Overall, our results demonstrate the importance of understanding the...
Differential Diagnosis of Waldenström's Macroglobulinemia | BLCTT
WM is a rare disorder with incidence reported to be approximately 3 per million people per year with 1000-1500 new cases diagnosed in the United States each year. WM is...
Conclusion/Relevance: Patient preference, clinical presentation, co-morbidities, molecular features, and treatment goals should be considered before choosing appropriate initial therapy for newly diagnosed WM. It is also essential to consider the financial toxicities of indefinite treatments such as oral BTK inhibitors and patients’ ability...
Advances in covalent drug discovery - Nature Reviews Drug Discovery
Source : https://www.nature.com/articles/s41573-022-00542-z
The rational discovery of covalent drugs depends on an expanding toolset of techniques. Here, Daniel Nomura and colleagues highlight covalent drugs that have achieved success over the past decade and...
Conclusion/Relevance: This Review showcases covalent drug discovery milestones with emphasis on the lessons learned from these programmes and how an evolving toolbox of covalent drug discovery techniques facilitates success in this field.
An 81-Year-Old Man with a 6-Year History of Chronic Lymphocytic Leukemia Presenting with Disease Flare Following Ibrutinib Discontinuation - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/36016481/
BACKGROUND Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm and the most common leukemia in adults in Western countries. Novel agents, including BTK inhibitors and the BCL2 inhibitor venetoclax,...
Conclusions: Our report highlights the problem of disease flare after ibrutinib discontinuation in order to avoid associated patient morbidity, underscoring the importance of awareness of this phenomenon and focusing on the addition of venetoclax at time of progression in ibrutinib-treated patients, as a temporary overlap strategy, to prevent...