K115

K-115, an isoquinolinesulfonamide compound, is a highly selective and potent (IC50 = 31 nM) Rho-kinase inhibitor; is in Phase II clinical development in patients with POAG or ocular hypertension.
IC50 value: 31 nM [1]
Target: ROCK inhibitor
K-115 had selective and potent inhibitory effects on ROCKs. In rabbits, topical instillation of K-115 significantly reduced IOP in a dose-dependent manner. Maximum IOP reduction was observed 1?h after topical instillation, which was 8.55?±?1.09?mmHg (mean?±?SE) from the baseline IOP at 0.5%. In monkeys, maximum IOP reduction was observed 2?h after topical instillation, which was 4.36?±?0.32?mmHg from the baseline IOP at 0.4%, and was significantly stronger than that of 0.005% latanoprost. Whole-head autoradiography showed that the radioactivity level was maximum at 15?min after instillation of [(14)C]K-115 in the ipsilateral eye [3].
NC-induced oxidative stress, including oxidation of lipids and production of ROS, was significantly attenuated by K-115. Furthermore, expression of the Nox gene family, especially Nox1, which is involved in the NC-induced ROS production pathway, was dramatically reduced by K-115 [4].