title: Ribosomal S6 kinase (RSK) modulators: a patent review.
abstract: BACKGROUND
  The p90 ribosomal S6 kinases (RSK) are a family of Ser/Thr protein kinases that are downstream effectors of MEK1/2-ERK1/2. Increased RSK activation is implicated in the etiology of multiple pathologies, including numerous types of cancers, cardiovascular disease, liver and lung fibrosis, and infections.
  
  
  METHODS
  The review summarizes the patent and scientific literature on small molecule modulators of RSK and their potential use as therapeutics. The patents were identified using World Intellectual Property Organization and United States Patent and Trademark Office databases. The compounds described are predominantly RSK inhibitors, but a RSK activator is also described. The majority of the inhibitors are not RSK-specific.
  
  
  CONCLUSIONS
  Based on the overwhelming evidence that RSK is involved in a number of diseases that have high mortalities it seems surprising that there are no RSK modulators that have pharmacokinetic properties suitable for in vivo use. MEK1/2 inhibitors are in the clinic, but the efficacy of these compounds appears to be limited by their side effects. We hypothesize that targeting the downstream effectors of MEK1/2, like RSK, are an untapped source of drug targets and that they will generate less side effects than MEK1/2 inhibitors because they regulate fewer effectors.
authors.affiliation: a Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , TN , USA.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Ludwik
authors.affiliation: a Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , TN , USA.|b Department of Cancer Biology , Vanderbilt University , Nashville , TN , USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lannigan
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2
keywords: BIX 02565; FMK; RSK; SL0101; p90RSK