Rho kinase inhibitors: a patent review (2014 – 2016)

ABSTRACT

Introduction: The Rho-kinases (ROCK), ROCK1 and ROCK2, are potent, widespread biochemical modulators which have been extensively studied. Due to the involvement of ROCKs in multiple biological processes, ROCK inhibitors have pleiotropic actions and may be of relevance for a number of therapeutic applications. The drawback is however that their use might be limited by occurrence of side effects.

Areas covered: Since the publication of the latest review in 2014, there have been significant advances in the field of ROCK inhibitors. In this paper we reviewed the patents published between September 2013 and September 2016. Recent novel molecules will be described. and progress from the compounds series described in the previous review as well as any new expected therapeutic uses for ROCK inhibitors that popped up in the last three years will be examined.

Expert opinion: While a number of potential applications in human for ROCK inhibitors have been reported, very few molecules are currently available to patients. In addition to fasudil, ripasudil (K-115, Kowa) was only recently approved in Japan for the treatment of glaucoma (2014). Notwithstanding some failures and subsequent discontinuation, the Pipeline of preclinical and clinical ROCK inhibitors remains significant.

KEYWORDS:

• Isoform selectivity
• ROCK
• ROCK inhibitor
• soft drugs

Article highlights

• New original scaffolds have been used to generate novel ROCK inhibitors

• ROCK2 isoform selective inhibitor is emerging as a potential breakthrough for systemic uses with minimal hypotensive effects

• Development of soft ROCK inhibitors remains an important strategy to circumvent systemic side-effects of pan-isoform specific inhibitors

• Progress in the field opens new applications such as CNS and oncology

This box summarizes key points contained in the article.

Declaration of interest

O Defert is an independent manager and S Boland is a former employee of Amakem Therapeutics NV. 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.

Additional information

Funding

There is no funding to declare.