LX7101 is a potent inhibitor of LIMK and ROCK2 with IC 50 values of 24, 1.6 and 10 nM for LIMK1 , LIMK2 and ROCK2 , respectively; also inhibits PKA with an IC 50 less than 1 nM.
In Vitro
LX7101 is a dual LIM-kinase and ROCK inhibitor for the treatment of ocular hypertension and associated glaucoma. LX-7101 also displays potent inhibition of Akt1 with an IC 50 of less than 1 nM. The overall selectivity of LX7101 for LIMK2 increases at the higher physiological ATP concentrations. Under physiological conditions, the activity of LX7101 is primarily due to inhibition of LIMK2. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
LX-7101 is advanced to Phase-I clinical trials as an intraocular pressure (IOP)-lowering agent for treatment of glaucoma. LX-7101 displays a significant IOP reduction at time points ranging from 1 h to 6 h post administration in rabbits . Topical doses of LX-7101 are evaluated for tolerability on the eyes of mice, rats, and rabbits. It is well tolerated at doses up to 0.5% in non-GLP single dose studies. In the mouse IOP assay, LX-7101 (5%) achieved additional reduction of IOP (5.0 mmHg total reduction) compared to the 0.1% formulation and demonstrated a long duration of action, with IOP not returning to baseline until more than 8 h postdose. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
