Inhibitors targeting Bruton’s tyrosine kinase in cancers: drug development advances

Abstract

Bruton’s tyrosine kinase (BTK) inhibitor is a promising novel agent that has potential efficiency in B-cell malignancies. It took approximately 20 years from target discovery to new drug approval. The first-in-class drug ibrutinib creates possibilities for an era of chemotherapy-free management of B-cell malignancies, and it is so popular that gross sales have rapidly grown to more than 230 billion dollars in just 6 years, with annual sales exceeding 80 billion dollars; it also became one of the five top-selling medicines in the world. Numerous clinical trials of BTK inhibitors in cancers were initiated in the last decade, and ~73 trials were intensively announced or updated with extended follow-up data in the most recent 3 years. In this review, we summarized the significant milestones in the preclinical discovery and clinical development of BTK inhibitors to better understand the clinical and commercial potential as well as the directions being taken. Furthermore, it also contributes impactful lessons regarding the discovery and development of other novel therapies.

Imidazoles as Potential Anticancer Agents: An Update on Recent Studies

“…Thus, Bcr-Abl and BTK are important targets against leukemia. Drugs, such as imatinib, nilotinib (4), and ponatinib (5), are known to target Bcr-Abl, while ibrutinib targets the BTK pathway (please see Reference [66] for a review of Bcr-Abl inhibitors and Reference [67] for a review of anticancer drugs targeting BTK). Bertrand et al synthesized 2,6,9-trisubstituted purine derivatives as candidate dual Bcr-Abl/Btk inhibitors [68].…”

Repurposing of Anticancer Drugs Expands Possibilities for Antiviral and Anti-Inflammatory Discovery in COVID-19

“…Bruton tyrosine kinase (BTK) inhibitors are approved therapies for treating lymphoid blood disorders such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), or Waldenstrom's disease (53). The SARS-CoV-2 virus can generate an overactivation of immune cells, including both B and T cells, leading to a "cytokine storm" thus contributing to acute lung injury and respiratory distress (21).…”

Onco-hypertension: Overview of hypertension with anti-cancer agents

“…BTK is downstream of the B cell receptor, and abnormal activation of this pathway in malignant B cells leads to cell survival, proliferation, and migration. 77 Inhibition of BTK interrupts this pathway and leads to reduced growth and survival of cancer cells. Ibrutinib is strongly associated with hypertension.…”