Therapy based on Bruton's tyrosine kinase (BTK) inhibitors one of the major treatment options currently recommended for lymphoma patients. The first generation of BTK inhibitor, Ibrutinib, achieved remarkable progress in the treatment of B-cell malignancies, but still has problems with drug-resistance or off-target induced serious side effects. Therefore, numerous new BTK inhibitors were developed to address this unmet medical need. In parallel, the effect of BTK inhibitors against immune-related diseases has been evaluated in clinical trials. This review summarizes recent progress in the research and development of BTK inhibitors, with a focus on structural characteristics and structure-activity relationships. The structure-refinement process of representative pharmacophores as well as their effects on binding affinity, biological activity and pharmacokinetics profiles were analyzed. The advantages and disadvantages of reversible/irreversible BTK inhibitors and their potential implications were discussed to provide a reference for the rational design and development of novel potent BTK inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2021.113329 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CDK1 inhibitor RO-3306 enhances BTKi potency in diffuse large B-cell lymphoma by suppressing JAK2/STAT3 signaling.
Int J Biol Macromol
January 2025
Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu Province, PR China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, Jiangsu Province, PR China. Electronic address:
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, which characterized by a high degree of heterogeneity in terms of clinical presentation, molecular phenotype, and genetic features. However, approximately 30 %-40 % of patients are refractory to standard chemotherapy, and their prognosis is poor. The emergence of small-molecule inhibitors, such as Bruton's tyrosine kinase inhibitors (BTKi), has greatly improved the treatment of DLBCL; however, drug resistance associated with small-molecule inhibitors has greatly limited their clinical application.
View Article and Find Full Text PDFBTK inhibitors (BTKi) are an established standard of care in CLL. The covalent BTKi ibrutinib, acalabrutinib and zanubrutinib bind to BTK C481 and are all susceptible to the C481S mutation. Non-covalent BTKi including pirtobrutinib overcome C481S resistance but are associated with multiple variant (non-C481) BTK mutations, including those associated with resistance to acalabrutinib and zanubrutinib (T474 codon and L528W mutations).
View Article and Find Full Text PDFChronic Lymphocytic Leukemia Care and Beyond: Navigating the Needs of Long-Term Survivors.
Cancers (Basel)
January 2025
Department of Hematology, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK.
Chronic lymphocytic leukemia (CLL) treatment has undergone a significant evolution with a shift from historical chemotherapeutic regimens to targeted therapies such as Bruton tyrosine kinase (BTK) and BCL-2 inhibitors. These advancements have been associated with a notable improvement in survival rates with a transformation of CLL into a chronic and manageable condition for most persons with this disease. However, as a consequence of improved outcomes, long-term CLL survivors now face emergent challenges which include a risk of infections, cardiovascular complications, and secondary malignancies.
View Article and Find Full Text PDFBTK inhibition in primary central nervous system lymphoma: mechanisms, clinical efficacy, and future perspectives.
Front Oncol
December 2024
Thoracic Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
The prognosis of primary central nervous system lymphoma (PCNSL) patients is relatively poor, and there is currently no standard treatment plan. Most patients choose high-dose chemotherapy based on methotrexate. While traditional chemotherapy combined with biological therapy has achieved limited results, some patients still do not respond to treatment or cannot tolerate its toxicity and side effects.
View Article and Find Full Text PDFPrognostic factors in chronic lymphocytic leukaemia - the old, the new and the future.
Leuk Lymphoma
January 2025
Lymphoma Service - The Alfred Hospital, Melbourne, Victoria, Australia.
Prognostic assessment in chronic lymphocytic leukemia (CLL) is essential for delivery of timely, personalized therapy. status, karyotype, IGHV mutational status, minimal residual disease (MRD), gene mutations and markers of cell proliferation were important prognostic tools in the era of chemo-immunotherapy (CIT). With BCL2 inhibitors (BCL2i), outcome is still impacted by IGHV status, status, complex karyotype, and achievement of undetectable MRD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!