ATP-citrate lyase (ACLY) inhibitors as therapeutic agents: a patenting perspective

ABSTRACT

Introduction

ATP citrate lyase (ACLY) is a key enzyme in cellular metabolism, being the main source of acetyl-Coenzyme A, an important precursor for fatty acid, cholesterol, and isoprenoid biosynthesis, and it is also involved in protein acetylation. Its expression changes are related to hyperlipidemia and cardiovascular diseases. Other studies have shown that ACLY is closely related to the occurrence of cancer: the increase in lipid synthesis provides the necessary building blocks for cell growth and division. Therefore, finding effective ACLY inhibitors has very important application prospects for lipid-related pathologies and cancer.

Areas covered

This review covers patents concerning ACLY inhibitors and alternative strategies to modulate ACLY activity, with their potential therapeutic applications.

Expert opinion

In recent years, ACLY as a drug target has become a hot spot in the research of innovative drugs for disorders of glucose and lipid metabolism. Many types of small-molecule ACLY inhibitors have been discovered, but few ACLY inhibitors proved to be highly effective in vitro and in vivo, since their main limitations were low cell penetration and low affinity to ACLY. The search for new effective ACLY inhibitors is of great significance and has broad application prospects for the treatment of hyperlipidemia and cancer.

KEYWORDS:

• ATP citrate lyase
• cancer
• lipid metabolism
• inhibitors

Article highlights

• ACLY plays an essential role in glucose and lipid metabolism as well as in cancer growth.

• ACLY inhibition can have important therapeutic implications for treating a wide range of diseases including hypercholesteremia, cardiovascular diseases, obesity, diabetes, metabolic syndrome and cancer.

• This review focuses on patented synthetic and natural ACLY inhibitors and their therapeutic applications.

• Patented alternative strategies to modulate ACLY activity are described.

• Expert opinion of future directions in the field of ACLY inhibition is reported.

Declaration of interests

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 paper was not funded.