Translocator protein (TSPO) ligands for the diagnosis or treatment of neurodegenerative diseases: a patent review (2010–2015; part 1)

ABSTRACT

Introduction: The translocator protein (TSPO) is an emerging target in diverse neurodegenerative diseases. Up-regulated TSPO in the central nervous system (CNS) appears to be involved in neuroinflammatory processes; therefore, the development of potent TSPO ligands is a promising method for alleviating or imaging patients with neurodegenerative diseases.

Areas covered: This review will provide an overview of recently developed TSPO ligands patented from 2010 to 2015. Part 1 will present a summary focusing on TSPO ligands other than indole-based or cholesterol-like compounds, which will be discussed in part 2. Part 1 covers diverse benzodiazepine-derived analogues such as isoquinoline carboxamides and aryloxyanilides. Moreover, bicyclic ring structures such as imidazopyridine, pyrazolopyrimidine, and phenylpurine will be highlighted as promising scaffolds for TSPO ligands. A brief analysis of currently reported TSPO structures will also be covered in part 1.

Expert opinion: Although the underlying pharmacological mechanism of TSPO remains to be elucidated, several TSPO ligands have shown therapeutic efficacy in experimental animal models of neurodegenerative diseases. In addition, radioactive TSPO ligands have been extensively studied for the diagnosis of neurodegenerative processes. Thus, further studies on both the basic and applied mechanisms of TSPO are warranted in the pursuit of successful pharmacological applications of TSPO ligands.

KEYWORDS:

• TSPO
• PBR
• neurodegenerative disease
• neuroinflammation
• PK 11195
• Ro5-4864
• emapunil
• alpidem
• DAA1106
• PBR28

Article highlights

• TSPO is an emerging target protein located in the mitochondria that functions in crucial biochemical processes such as apoptosis, respiration, ATP production, and ROS generation.

• Recent reports of TSPO structures can inform the predicted binding modes of TSPO ligands at a preclinical stage of development.

• TSPO ligands can be used to treat or diagnose patients with diverse brain diseases.

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 work was supported by the National Research Council of Science & Technology (NST) grant by the Korea government (MSIP) (No. CRC-15-04-KIST, 2N41660). This work was also supported by Korea Institute of Science and Technology (Grant: 2E26650).