Nitric oxide (NO) is an endogenous gas signaling molecule that inhibits aqueous production and increases aqueous outflow from the atrium, thereby reducing IOP. Regarding the role of NO in controlling IOP in glaucoma, it has been demonstrated in human patients and animal models. Therefore, NO donating anti-glaucoma drugs have a broad research potential.
For glaucoma treatment, Ace Therapeutics provides services for the development of NO-mediated next-generation anti-glaucoma drugs, using some novel NO-donating compounds or candidate molecules for glaucoma treatment to achieve synergistic IOP management.
NO and Glaucoma
NO is synthesized from three isomers of NO syntheses (NOS). It is a colorless, odorless gas-conducting substance and a highly active free radical molecule that performs extremely important physiological and pathological functions. TM, SC cells, the ciliary body and the iris sphincter of the anterior chamber angle express NOS, which are associated with the regulation of blood flow and the outflow of aqueous humor.
NO-mediated glaucoma treatment has several mechanisms of action. First, NO promotes conventional aqueous drainage. NO causes TM and SC relaxation and increases outflow through a series of actions as shown in the schematic. NO inhibits aqueous humor production by inhibiting enzymes involved in ciliary processes to reduce aqueous secretion. NO regulates ocular blood flow and has a neuroprotective effect, protecting the RGC and axons from damage.
Fig. 1 Summary of the mechanism of action of NO-mediated glaucoma treatment. (Yu-Jie M A O, et al., 2020)
Solutions of NO-Mediated Therapy Development for Glaucoma
We provide solutions for NO-mediated glaucoma-based treatment by covalent linking various conventional drugs for glaucoma treatment to NO-releasing groups via linker, and are committed to developing new drugs that are highly effective and long-lasting. The specific effect is that upon administration, the drug breaks down into glaucoma drug and NO, producing a synergistic anti-glaucoma effect.
Table 1. Our specific solutions for NO donating anti-glaucoma drugs for glaucoma.
| Development Strategies | Our Solutions |
|---|---|
| NO-prostaglandin analogs | Our solution is based on the structure of prostaglandins and the development of NO-donated prostaglandin analogs that synergistic-ally combat glaucoma through two different IOP-lowering mechanisms. Among them, prostaglandin analogs target nine different subtypes of receptors in the eye and exert their main physiological activity as ester prodrugs. The effects of the NO molecule can be directly observed in animal models such as rabbits, dogs, and mice. |
| NO donating β-adrenergic receptor antagonists | Our solution is to develop a novel set of NO-donating β-adrenergic receptor antagonists derivatives. We used trigger release strategy to design new derivatives that trigger the release of NO donor molecules and produce drugs. |
| NO donating carbonic anhydrase inhibitors | We work to modify NO donors to provide compounds that show good CA enzyme activity. |
| Other NO donating anti-glaucoma molecules | We provide services for the development of other drugs such as NO-donating antioxidant mixtures and delivery of large molecules of NO, mainly providing innovative strategies for improving the bio-availability of NO. |
What We Provide
- Innovative solutions
- Expertise in NO donating and other technologies
- Synthesis and evaluation of candidate compounds
- Detailed non-clinical studies
- Powerful preclinical data
- Continuous release delivery success stories
Ace Therapeutics is an international glaucoma research company dedicated to developing innovative solutions to help improve glaucoma treatment. We are developing a broad portfolio of novel drug candidates for glaucoma, please contact us with any ideas you may have.
Reference
- Yu-Jie M A O, et al. Nitric oxide donating anti-glaucoma drugs: advances and prospects. Chinese journal of natural medicines, 2020, 18(4): 275-283.