Bruton’s tyrosine kinase (BTK) inhibitors in treating cancer: a patent review (2010-2018)

ABSTRACT

Introduction: Bruton’s tyrosine kinase (BTK) plays a critical role in the regulation of survival, proliferation, activation and differentiation of B-lineage cells. It participates by regulating multiple cellular signaling pathways, including B cell receptor and FcR signaling cascades. BTK is abundantly expressed and constitutively active in the pathogenesis of B cell hematological malignancies, as well as several autoimmune diseases. Therefore, BTK is considered as an attractive target for treatment of B-lineage lymphomas, leukemias, and some autoimmune diseases. Many industry and academia efforts have been made to explore small molecular BTK inhibitors.

Areas covered: This review aims to provide an overview of the patented BTK inhibitors for the treatment of cancer from 2010 to 2018.

Expert opinion: BTK inhibitors attract much interest for their therapeutic potential in the treatment of cancers and autoimmune diseases, especially for B cell hematological malignancies. In 2013, ibrutinib was approved by the FDA as the first-in-class BTK inhibitors for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), and now it is also undergoing clinical evaluation for other indications in either single or combined therapy. It is clear that BTK inhibitors can provide a promising clinical benefit in treating B-lineage lymphomas and leukemias.

KEYWORDS:

• BTK inhibitors
• B cell receptor
• lymphomas and leukemias
• patent

Article highlights

1. BTK is an attractive target for the treatment of B-lineage lymphomas and leukemias, and some autoimmune diseases. BTK inhibitors can be classified as irreversible inhibitors and reversible inhibitors according to their binding mode with the BTK catalytic domains. Now, great efforts by industry and academics are being made to develop both irreversible and reversible BTK inhibitors.

2. This review covers the recent patent literature (2010–2018) on BTK inhibitors, highlighting the representative structures and their available data.

3. Expert opinion is given regarding the future of the development of novel BTK inhibitors.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they served on advisory boards for Janssen and Pharmacyclics. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The paper was funded by the National Natural Science Foundation of China (81602967 and 81402792).