Patent landscape for discovery of promising acyltransferase DGAT and MGAT inhibitors

ABSTRACT

Introduction

DGAT and MGAT enzymes play an important role in triacylglycerol (TGA) biosynthesis. Overexpression of these enzymes may lead to accumulation of TGA in adipose tissues causing development of diseases such as obesity and diabetes. High triglyceride levels increase risk factors for atherosclerosis, and increase the risk of heart attack, stroke and other heart diseases. DGAT and MGAT inhibitors are used for the treatment of such metabolic diseases. A number of DGAT and MGAT inhibitors entered into clinical and preclinical stages. However, some adverse effects are associated with them. Thus there is need to develop new, potent and safe DGAT and MGAT inhibitors.

Area covered

In this review, the authors carefully searched patent literature and reviewed recent advances since the year 2014. Diverse chemical classes reported in the patents belonging to the category DGAT and MGAT inhibitors have been highlighted.

Expert opinion

DGAT and MGAT inhibitors are now gaining significant importance in the treatment of metabolic diseases. Fused heterocycles with a combination of aromatic and aliphatic hydrophobic substituents could offer more potent DGAT and MGAT inhibitors. Previously reported chemical scaffolds and their DGAT and MGAT inhibitory activity could be employed as an input for some in silico studies to discover novel, potent and safe DGAT and MGAT inhibitors.

KEYWORDS:

• Diacylglycerol acyltransferase
• monoacylglycerol acyltransferases
• DGAT/MGAT inhibitors
• obesity
• diabetes

Article highlights

• The obesity and diabetes are major concern worldwide.

• High blood triglyceride levels lead to coronary heart disease, stroke and pancreatitis.

• Inhibiting specific isoforms i.e. DGAT1, DGAT2, MGAT2 selectively is an attractive strategy for treating metabolic diseases.

• Advances in DGAT and MGAT inhibitors since 2014 have been discussed in the article.

• The review covers discovery of DGAT1, DGAT2 and MGAT2 inhibitors patented by pharmaceutical companies.

• DGAT and MGAT inhibitors are characterized by hydrophobic parameter introduced by a combination of aromatic and aliphatic lipophilic substituents.

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 paper was not funded.