Glaucoma is a complex progressive optic nerve disease. Currently, elevated intraocular pressure (IOP) due to obstruction of atrial aqueous (AH) outflow remains the only modifiable risk factor. Rho kinase (ROCK) inhibitors have been identified as glaucoma therapeutic agents that can reduce IOP in glaucoma.
ROCK inhibitors target TM tissue and increase AH drainage to slow damage to the optic nerve. For ROCK inhibitors, Ace Therapeutics provides development services for scientists and pharmaceutical companies working to design and develop novel molecular scaffolds to improve drug efficacy and stability.
The Structure and Mechanism of ROCK in Glaucoma
ROCK plays a major role in mediating cytoskeletal rearrangements via the Rho signaling pathway. Active ROCK phosphorylates many substrates and serves many cellular roles, including cell migration, proliferation, phagocytosis and apoptosis. A role for cytoskeletal activators in the regulation of AH efflux resistance has been demonstrated, including ROCK inhibitors, which can reduce AH efflux resistance.
The ability of ROCK inhibitors to promote AH outflow is attributed to an increase in cell permeability through an effect on the TM cytoskeleton, thereby reducing the resistance to AH outflow. They also offer the potential for antioxidant and neuroactive protection, with beneficial effects on glaucoma. In conclusion, the development of ROCK inhibitor-based IOP-lowering therapies is a proven and promising glaucoma drug.
Fig. 1 Efficacy of ROCK inhibitors in the treatment of glaucoma. (Al-Humimat G, et al., 2021)
Solutions of Rho Kinase Inhibitor Development for Glaucoma
ROCK inhibitors have been identified as therapeutic agents for glaucoma. In recent years, some progress has been made in the field of treating glaucoma. For example, Netarsudil, Ripasudil, etc., these are small molecule ROCK inhibitors that have been developed and applied for the treatment of glaucoma.
We can use some of the newly reported molecules or directly develop new molecules to provide anti-glaucoma drug development as well as to study their specific biological effects affecting the ROCK pathway.
Table 1. Our specific solutions for ROCK inhibitor for glaucoma.
| Development Strategies | Our Solutions |
|---|---|
| Fasudil | The molecule is used for the treatment of various vascular diseases and has shown a hypotensive effect on IOP in a model of hypertension. Our solution is to design and modify the molecular structure to develop potent ROCK inhibitors, providing all trial services from drug development to preclinical study phase. |
| Verosudil | This is a dual selective ROCK inhibitor with ROCK1/ROCK2 activity. We develop this dual inhibitor with the aim of optimizing the efficacy and improving the safety of ROCK inhibitor drugs. |
| Latrunculin-B | It is a unique marine toxin that achieves its therapeutic purpose by altering the structural changes in TM cells. It is also a ROCK inhibitor. We can provide an evaluation of its safety and efficacy for further use in development. |
| LX7101 | It is a dual inhibitor of LIM kinase (LIMK) and ROCK. For the dual inhibitors, we can design and characterize their effective inhibition and validate the IOP-lowering and therapeutic effects and other effects of these molecules. |
| Other molecular drug programs | Identify and design promising ROCK inhibitors and validate their efficacy and safety. |
Our Goals
- Reduce the adverse effects and improve the stability of the associated ROCK inhibitors.
- Improve the specificity of next-generation ROCK inhibitors to target cells.
- Add other pathways of action to improve efficacy.
The market for glaucoma drugs is booming, and as science and technology evolve, we continue to provide support for the development and improvement of ROCK inhibitor drugs for glaucoma. If your glaucoma program still needs the assistance of a partner, please contact us.
References
- Al-Humimat G, et al. Investigational Rho Kinase Inhibitors for the Treatment of Glaucoma. J Exp Pharmacol, 2021, 25;13:197-212.
- Saha B C, et al. Status of Rho kinase inhibitors in glaucoma therapeutics—an overview. Int Ophthalmol, 2022, 42, 281–294.