Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. The current therapeutic goal of the main ocular drugs is to lower IOP. One of the main treatment options is carbonic anhydrase inhibitors (CAIs), which lower IOP in patients with glaucoma by decreasing the rate of bicarbonate formation and thus atrial fluid secretion. Ace Therapeutics is dedicated to uncovering new targets and actions of CAIs, helping researchers to design novel and selective inhibitors and exploring the pharmacological activity of CAIs in vitro and in vivo.
Carbonic Anhydrase Inhibitors in Glaucoma
Carbonic anhydrase (CA) is an enzyme that represents a very general system of metalloenzymes. CAs are involved in many physiological actions, such as the secretion of body fluids, and they play an important role in the regulation of these processes. CAs also play an important role in the pathophysiology of glaucoma. This is because isoforms of CAs have been identified in ocular tissues and are responsible for the secretion of bicarbonate, which affects aqueous humor secretion.
Therefore, CAIs are one of the most important classes of drugs for the treatment of glaucoma. Several molecular drugs have been developed to date to inhibit carbonic anhydrase isoforms. We list some of the CAI drugs that have been developed and applied, as shown in the table below.
Table 1. Information about carbonic anhydrase inhibitors for glaucoma.
| Category | Inhibitor Name | Treatment Mechanism |
|---|---|---|
| Systemic CAIs | Acetazolamide | Sulfonamides inhibit carbonic anhydrase, thereby inhibiting HCO3- production. The inhibition of HCO3- reduces aqueous humor formation and decreases IOP in glaucoma patients. |
| Dorzolamide | To treat elevated intraocular pressure in primary open-angle glaucoma and hypertension. | |
| Brinzolamide | It is a highly specific, non-competitive, reversible and potent carbonic anhydrase II (CAII) inhibitor that is continuously released into the ciliary body to regulate aqueous humor. | |
| Ocular CAIs | Acetazolamide, dorzolamide, brinzolamide | To increase blood flow to the optic nerve papillae, induce relaxation of the ciliary artery, and improve ocular blood perfusion. |
Solutions of Carbonic Anhydrase Inhibitor Development for Glaucoma
The field of glaucoma drug discovery targeting CAIs has been very active for many years. The large number of isozymes with different physiological effects suggests the need to develop specific inhibitors against various isozymes. We are committed to the development of highly specific, selective enzyme inhibitors as glaucoma drugs.
- Drug Design
Firstly, we identify different CA isoforms and study their functions in a variety of physiological processes to select and demonstrate suitable targets for glaucoma pathological conditions. To design CAIs with good aqueous solubility and IOP reduction for the target, appropriate moieties or scaffolds can be attached chemically. Novel drug directions that can be investigated include novel sulfonamides, monothiocarbamates, dithiocarbamates, etc. - Molecule Synthesis
We can use the reagents and conditions described in the standard protocol for the synthesis of the designed molecules. - In Vitro and In Vivo Studies
We evaluate the inhibitory effect of synthetic compounds against isoform CA, evaluate in vivo IOP-lowering activity in various experimental animal models of glaucoma and perform in vitro toxicity assessment by performing cell viability assays.
Our Development Standards
- Inhibitors almost completely eliminate CA activity at certain concentrations.
- Design novel selective inhibitors with the desired therapeutic properties.
- Proper suppression analysis and assessment.
- Discuss the in vitro and in vivo pharmacological activities of various CAIs.
We look forward to working with you to get new drugs that exceed expectations.
Reference
- Shahsuvaryan M L. Carbonic Anhydrase Inhibitors in Ophthalmology: Glaucoma and Macular Oedema. In: The Carbonic Anhydrases: Current and Emerging Therapeutic Targets. Progress in Drug Research, 2021.