PI3Kδ inhibitors for the treatment of cancer: a patent review (2015-present)

ABSTRACT

Introduction: PI3Kδ is an important subtype of PI3K kinases, which is mainly expressed in leukocytes and plays an important role in the proliferation, differentiation, maturation and self-reaction of B cells. It is an effective target in the treatment of hematological malignancies and autoimmune diseases such as rheumatoid arthritis. Therefore, many pharmaceutical companies and research institutions have focused on the PI3Kδ subtype in an attempt to develop potent and selective PI3Kδ inhibitors.

Areas covered: This review aims to provide an overview of the patented selective PI3Kδ inhibitors in treating cancer from 2015 to present.

Expert opinion: Due to the importance of PI3Kδ, the development of selective PI3Kδ inhibitors for the treatment of hematoma and autoimmune diseases is expected. On 23 July 2014, the world’s first selective PI3Kδ inhibitor, idelalisib, was approved by the FDA for the treatment of CLL, FL and SLL. Moreover, there are still many small molecule selective PI3Kδ inhibitors at different stages of development. The future research effort for development of PI3Kδ inhibitors is to manage the toxicity and lower the side-effects.

KEYWORDS:

• PI3Kδ inhibitors
• hematological malignancies
• autoimmune diseases
• idelalisib
• toxicity

Article highlights

• PI3Kδ has been identified as a promising target for treatment of hematoma and autoimmune diseases. Selective PI3Kδ inhibitors can be classified as propeller-type inhibitors and flat-type inhibitors. Now, great efforts from industry and academic institutions are underway to develop novel, potent and selective PI3Kδ inhibitors.

• This review covers the recent patent literature (2015 - present) on selective PI3Kδ inhibitors, highlighting the representative structures and their available data.

Expert opinion is given regarding the future of the development of novel and selective PI3Kδ inhibitors.

This box summarizes 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Natural Science Foundation of Shaanxi Province, China (2019JM-023). The authors also thank the Talent funding Program of Health Science Center, Xi’an Jiaotong University.