Galectin-1 inhibitors and their potential therapeutic applications: a patent review

ABSTRACT

Introduction: Galectins have affinity for β-galactosides. Human galectin-1 is ubiquitously expressed in the body and its expression level can be a marker in disease. Targeted inhibition of galectin-1 gives potential for treatment of inflammatory disorders and anti-cancer therapeutics.

Areas covered: This review discusses progress in galectin-1 inhibitor discovery and development. Patent applications pertaining to galectin-1 inhibitors are categorised as monovalent- and multivalent-carbohydrate-based inhibitors, peptides- and peptidomimetics. Furthermore, the potential of galectin-1 protein as a therapeutic is discussed along with consideration of the unique challenges that galectin-1 presents, including its monomer-dimer equilibrium and oxidized and reduced forms, with regard to delivering an intact protein to a pathologically relevant site.

Expert opinion: Significant evidence implicates galectin-1’s involvement in cancer progression, inflammation, and host-pathogen interactions. Conserved sequence similarity of the carbohydrate-binding sites of different galectins makes design of specific antagonists (blocking agents/inhibitors of function) difficult. Key challenges pertaining to the therapeutic use of galectin-1 are its monomer-dimer equilibrium, its redox state, and delivery of intact galectin-1 to the desired site. Developing modified forms of galectin-1 has resulted in increased stability and functional potency. Gene and protein therapy approaches that deliver the protein toward the target are under exploration as is exploitation of different inhibitor scaffolds.

KEYWORDS:

• Galectin-1
• carbohydrate
• inhibitor design
• patents

Article highlights

• The pathological effects of galectin-1 are dependent on the biological context.

• Significant correlation between the over-expression of galectin-1 and certain cancers underscores the relevance of galectin-1 antagonists as prospective anti-cancer reagents.

• Monovalent and multivalent inhibitors of galectin-1 function are underexplored with respect to their specificity and specific mechanisms of action.

• Galectin-1 can induce both pro- and anti-inflammatory effects through the regulation of immune cells.

• The use of galectin-1 as a therapeutic agent faces protein-specific challenges in addition to the poor pharmacokinetics of protein delivery.

This box summarizes key points contained in the article.

Declaration of interest

H. Blanchard gratefully acknowledges the financial support from the Cancer Council Queensland. The authors have no other 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 apart from those disclosed.