title: Rho kinase inhibitors: a patent review (2014 - 2016).
abstract: 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.
authors.affiliation: a Amakem Therapeutics NV , Agoralaan A Bis , Diepenbeek , Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Defert
authors.affiliation: a Amakem Therapeutics NV , Agoralaan A Bis , Diepenbeek , Belgium.|b Cistim , Gaston Geenslaan 2 , Leuven , Belgium.
authors.forename: Sandro
authors.initials: S
authors.lastname: Boland
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007546:Isoquinolines; C584679:K-115; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C049347:fasudil
keywords: Isoform selectivity; ROCK; ROCK inhibitor; soft drugs