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  • Writer's pictureDr Edin Hamzić

⚗️ What Are Bruton Tyrosine Kinase (BTK) Inhibitors?

Updated: Jan 10


  • ⚠️In short, Bruton tyrosine kinase (Btk) inhibitors inhibit the Bruton tyrosine kinase activity, and this characteristic of Btk inhibitors makes them as ideal for the treatment of several B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and Waldenström macroglobulinemia (WM).

  • ℹ️ But let’s deconstruct and explain all the critical terms in the above sentence to fully understand what Bruton tyrosine kinase (Btk) inhibitors are. To do that, we have to answer the following questions:

    • What Are Protein Kinases?

    • What Are Tyrosine Kinases?

    • What Is Bruton Tyrosine Kinase (BTK)?

    • What Are Tyrosine Kinase Inhibitors?

    • What Is Bruton Tyrosine Kinase (BTK)?

  • Here, I assume that you, the reader, know what an enzyme and phosphorylation are.

What Are Protein Kinases?

  • ℹ️ Protein kinases are a class of enzymes that catalyze the phosphorylation of proteins and consequently alter the activity of the substrate (substance being catalyzed by the protein kinase) or capacity of the substrate to interact with other proteins.

  • ℹ️ Protein kinases are crucial elements of kinase signaling pathways. Kinase signaling pathways represent the most common form of reversible post-translational modifications that control many aspects of cellular function or put in simple terms to communicate key information within a cell.

  • ℹ️ Non-normal activation of protein kinases is the main sign of malignancies, that include changes in cellular proliferation, survival, motility, and metabolism, angiogenesis, and evasion of the anti-tumor immune response.

What Are Tyrosine Kinases?

In the human genome, there are roughly 500 genes that encode different types of protein kinases, (explained above) and protein kinases can be divided into two main groups:

  1. ℹ️ Serine/threonine kinases phosphorylate the hydroxyl groups of serines and threonines in their targets. Serine/threonine kinases constitute the majority of all protein kinases.

  2. ℹ️ The other group is tyrosine kinases that transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. Tyrosine kinases are basically "on"/ "off" switches in many important cellular functions.

The tyrosine kinases can further be divided into two largest families:

  1. Receptor tyrosine kinases are the transmembrane receptor-linked kinases

  2. Non-receptor tyrosine kinases that are cytoplasmic proteins

What Is Bruton Tyrosine Kinase (Btk)?

  • ⚠️ Bruton’s tyrosine kinase (Btk) is a member of a group of cytoplasmic, non-receptor tyrosine kinases that play a critical role in the development and functioning of the immune system.

  • ℹ️ Bruton’s tyrosine kinases are member of the Tec family of kinases, which are non-receptor tyrosine kinases. Btk is primarily expressed in B cells, a type of white blood cell that is essential for the adaptive immune system.

  • ℹ️ The BTK gene that encodes Bruton’s tyrosine kinase (Btk) is located on the X chromosome and mutations in Btk lead to defective maturation and development of B cells, which is the main cause of the X-linked agammaglobulinemia (XLA) disorder. Actually, this is how the Bruton tyrosine kinase was initially identified and described by describing mutation in a novel non-receptor protein tyrosine kinase mutation that was responsible for human X-linked agammaglobulinemia (XLA) disease.

  • ℹ️ This mutation that causes X-linked agammaglobulinemia produces as a result the reduced numbers of mature B cells that lead to the development of XLA immunodeficiency syndrome. The condition is manifested in predominantly young male patients who have frequent severe infections and exhibit nearly complete loss of B cells and dramatically decreased levels of immunoglobulins in the bloodstream.


Why Is Bruton Tyrosine Kinase Important?

  • ⚠️So, many studies have established that Btk is crucial for B-cell development, differentiation, survival, and signal transduction.

  • ℹ️ On the other side, results from a number of studies showed that Btk’s signaling role is critical to the survival of B-cell leukemia and lymphoma cells. These studies provide the rationale for targeting BTK in treating B-cell malignancies.

  • ℹ️ By targeting the B-cell receptor pathway via the inhibition of Bruton tyrosine kinase (BTK), it is possible to treat a variety of B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia.

What Is Bruton Tyrosine Kinase (BTK) Inhibitor?

  • ⚠️In short, Bruton tyrosine kinase (Btk) inhibitors inhibit the Bruton tyrosine kinase activity, and this characteristic of Btk inhibitors makes them an ideal target for the treatment of several B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and Waldenström macroglobulinemia (WM).

What Are FDA-Approved BTK Inhibitors?

  • Currently, there are three Btk inhibitors approved by the U.S. Food and Drug Administration:

    • Ibrutinib (Imbruvica)

    • Acalabrutinib (Calquence), and

    • Zanubrutinib (Brukinsa).


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