Necroptosis inhibitors as therapeutic targets in inflammation mediated disorders - a review of the current literature and patents

ABSTRACT

Introduction: Recent studies have shown substantial interplay between the apoptosis and necroptosis pathways. Necroptosis, a form of programmed cell death, has been found to stimulate the immune system contributing to the pathophysiology of several inflammation-mediated disorders. Determining the contribution of necroptotic signaling pathways to inflammation may lead to the development of selective and specific molecular target implicated necroptosis inhibitors.

Areas covered: This review summarizes the recently published and patented necroptosis inhibitors as therapeutic targets in inflammation-mediated disorders. The role of several necroptosis inhibitors, focusing on specific signaling molecules, was discussed with particular attention to inflammation-mediated disorders. Data was obtained from Espacenet®, WIPO®, USPTO® patent websites, and other relevant sources (2006-2016).

Expert opinion: Necroptosis inhibitors hold promise for treatment of inflammation-mediated clinical conditions in which necroptotic cell death plays a major role. Although necroptosis inhibitors reviewed in this survey showed inhibitory effects against several inflammation-mediated disorders, only a few have passed to the stage of clinical testing and need extensive research for therapeutic practice. Revisiting the existing drugs and developing novel necroptosis inhibiting agents as well as understanding their mechanism are essential. A detailed study of necroptosis function in animal models of inflammation may provide us an alternative strategy for the development of drug-like necroptosis inhibitors.

KEYWORDS:

• Apoptosis
• immune system
• inflammation
• necroptosis
• reactive oxygen species
• RIPK1

Article highlights

• Role of necroptosis inhibitors attention to inflammation-mediated disorders has been described.

• Necroptosis inhibitors from various synthetic molecules, natural products, and derived compounds are provided.

• A review of the patent literature on necroptosis inhibitors over the past six years is provided.

• Drug repositioning concept can be used as a useful tool for the discovery of novel necroptosis inhibitors.

• To develop specific biomarkers for identifying necroptosis could provide new trends towards the therapy of necroptosis linked inflammation-mediated disorders.

• Detailed study of necroptosis function in animal models of inflammation may provide an alternative strategy for the development of drug-like necroptosis 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.

Additional information

Funding

This paper was supported by Konkuk University.