In the past few years, Bruton's tyrosine Kinase (Btk) has emerged as new target in medicinal chemistry. Since approval of ibrutinib in 2013 for treatment of different hematological cancers (as leukemias and lymphomas), two other irreversible Btk inhibitors have been launched on the market. In the attempt to overcome irreversible Btk inhibitor limitations, reversible compounds have been developed and are currently under evaluation. In recent years, many Btk inhibitors have been patented and reported in the literature. In this review, we summarized the (ir)reversible Btk inhibitors recently developed and studied clinical trials and preclinical investigations for malignancies, chronic inflammation conditions and SARS-CoV-2 infection, covering advances in the field of medicinal chemistry. Furthermore, the nanoformulations studied to increase ibrutinib bioavailability are reported.
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http://dx.doi.org/10.3390/ijms22147641 | DOI Listing |
Expert Opin Drug Saf
January 2025
Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Introduction: Bruton's tyrosine kinase (BTK) is a cytoplasmic signaling protein expressed across a variety of immune cells, terminally differentiated plasma cells, and natural killer cells. Due to the signal potential and targetable nature of BTK, the use of BTK inhibitors (BTKis) has been proposed for the management of several diseases. Currently, the use of BTKis is under investigations for several dermatological conditions such as pemphigus, systemic lupus erythematosus, hidradenitis suppurativa, atopic dermatitis, and chronic spontaneous urticaria (CSU).
View Article and Find Full Text PDFAm J Hematol
January 2025
Department I of Internal Medicine and Medical Faculty, University of Cologne, Köln, Germany.
Disease Overview: Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Division of Hematology and Medical Oncology, University of Washington, Seattle, WA 98195, USA.
Pathway inhibitors targeting Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) have dramatically changed the treatment landscape for both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL). However, with increased utilization, a growing number of patients will experience progressive disease on both agents. This subgroup of "double refractory" patients has limited treatment options and poor prognosis.
View Article and Find Full Text PDFBlood Adv
January 2025
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States.
Some CLL patients who develop progressive disease (PD) during treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) acquire pathway resistance mutations in BTK or PLCG2. Here, we report gene mutation data from paired baseline and PD peripheral blood samples from 52 patients (zanubrutinib, n=24; ibrutinib, n=28) who, at an early median follow-up time of 25.7 months, progressed on zanubrutinib or ibrutinib treatment in the ALPINE trial (NCT03734016).
View Article and Find Full Text PDFAnn Hematol
January 2025
Service de Thérapie Cellulaire et d'Hématologie Clinique, CHU Estaing, Clermont-Ferrand, France.
The advent of BTK inhibitors has been transformative in the management of patients with chronic lymphocytic leukemia or other B-cell lymphoproliferative disorders. However, emergence of BTK or PLCG2 mutations lead to resistance to these compounds and are now a growing concern in clinical practice. Assessing BTK mutations is now becoming a priority to guide the therapeutic decision at further relapse.
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