IC50: <1 nM for ROCK-II

Chroman 1 is a highly potent ROCK-II inhibitor. ROCK is a member of the AGC kinase family of serine/threonine kinases that is comprised of two highly homologous isoforms, which are ROCK-I and ROCK-II.. As one of the downstream effectors of RhoA, ROCK regulates stress fiber formation and actin cytoskeletal organization via phosphorylation of myosin light chain. Currently, there is plenty of interest in the inhibition of Rho kinase (ROCK) to treat various diseases.

In vitro: Chroman 1 was found to be a sub-nanomolar ROCK-II inhibitor with excellent to moderate selectivity over related kinases studied as a preliminary assessment, such as AKT1, protein kinase A (PKA), and the highly homologous Cdc42-binding kinase. In addition, Chroman 1 also showed good in-vitro activity in the functional cell-based myosin light chain bis-phosphorylation assay [1].

In vivo: Pharmacokinetic evaluation in rats showed that Chroman 1 had moderately improved oral bioavailability (27–35%) relative to its lead compounds, which were benzodioxane and chroman. In addition, Chroman 1 also displayed an unique intriguing pharmacokinetic profile, which was with high systemic exposure through oral delivery [1].

Clinical trial: So far, there is no clinical study reported.

References:
[1] Chen YT,Bannister TD,Weiser A,Griffin E,Lin L,Ruiz C,Cameron MD,Schürer S,Duckett D,Schrter T,LoGrasso P,Feng Y.  Chroman-3-amides as potent Rho kinase inhibitors. Bioorg Med Chem Lett.2008 Dec 15;18(24):6406-9.