LX7101 is an effective inhibitor of LIMK and ROCK2 (IC50: 24, 1.6, and 10 nM for LIMK1, LIMK2, and ROCK2, respectively). It also inhibits PKA (IC50 <1 nM).

ROCK2:10 nM, LIMK1:24 nM, LIMK2:1.6 nM, PKA:1 nM

LX7101 is a dual LIM-kinase and ROCK inhibitor for treating ocular hypertension and associated glaucoma, showing effective inhibition of Akt1 (IC50<1 nM)[1]. Its primary activity is due to LIMK2 inhibition under physiological conditions[2], with enhanced selectivity for LIMK2 at higher physiological ATP concentrations.

Topical doses of LX-7101 are evaluated for tolerability in the eyes of mice, rats, and rabbits. It is well tolerated at doses up to 0.5% in non-GLP single-dose studies. LX-7101 is advanced to Phase-I clinical trials as intraocular pressure (IOP)-lowering agent for the treatment of glaucoma. LX-7101 shows a significant IOP reduction at time points ranging from 1 h to 6 h post-administration in rabbits[1]. LX-7101 (5%) achieved an additional reduction of IOP (5.0 mmHg total reduction) compared to the 0.1% formulation. It also demonstrated a long duration of action, in the mouse IOP assay, with IOP not returning to baseline until more than 8 h postdose[2].