Ligands for Ser/Thr phosphoprotein phosphatases: a patent review (2005-2015)

ABSTRACT

Introduction: The role played by phosphoprotein phosphatases (PPP) enzymes makes them of interest as therapeutic targets to treat pathologies including neurodegenerative diseases, cancer and autoimmune diseases, but also liable to cause severe side effects. This fact has hindered the study of PPP ligands as potential drugs. Fortunately, recent advances in the comprehension of PPP biochemistry have given rise to the development of refined pharmacological strategies to selectively target phosphatases and limit the possible generation of adverse reactions.

Areas covered: This review summarizes the most relevant patents claiming the use of PPP ligands to treat human diseases in the last decade (2005–2015). It also includes some pharmacological strategies aiming to indirectly modulate PPP functionality by interacting with PPP-regulating enzymes.

Expert opinion: There is still much work to be done to validate PPP enzymes as eligible targets for the development of new drugs. The most significant barrier is likely to be persuading the majority of the scientific community that PPP enzymes are not too unspecific. Few patents disclosed the rational design of direct PPP ligands, while many inventions relied on long chain peptides-based approaches. Overall, the future of ligands for PPP enzymes as therapeutics seems both challenging and exciting.

KEYWORDS:

• Ser/Thr phosphatases
• phosphoprotein phosphatases
• PP1
• PP2A
• PP2B
• PP3
• calcineurin
• PP5
• neurodegeneration
• cancer

Article highlights

• Phosphoprotein phosphatase enzymes catalyze the removal of phosphate groups from Ser and Thr protein residues.

• They work ubiquitously in a concerted manner with their counterparts kinase enzymes.

• Despite this essential role, they have not been considered eligible therapeutic targets for drug discovery, although their alteration has been documented in cancer or neurodegenerative diseases, among other pathologies.

• Some patents disclosed in the last decade point out that ligands for these enzymes could have clinical use.

• Much work remains to be done to validate phosphoprotein phosphatases as therapeutic targets, particularly the assessment of the possible side effects of their ligands.

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Financial and competing interests disclosure

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.