Intraocular pressure (IOP) is a major risk factor for glaucoma. Studies have demonstrated the great potential of prostaglandin (PG) receptors to control IOP. Current first-line drugs for the treatment of glaucoma are PG analogs, which stimulate intraocular PG receptors and lower IOP by primarily increasing aqueous outflow. Ace Therapeutics offers research services for the detailed exploration of different PG receptors, the development of drugs targeting prostaglandin receptors for glaucoma treatment and the evaluation of the potential of new drugs. We hope that new discoveries on PG may lead to more options for glaucoma drug therapy and to develop safer, more effective, and tolerable molecular drugs.
Anti-glaucoma Mechanism of Action of Prostaglandins
Prostaglandins are naturally occurring, biologically active polyunsaturated fatty acid derivatives consisting of 20 carbon atoms. In glaucoma, the basic mechanism of action of PG is to reduce IOP by increasing outflow from the TM and uveosclera. The expression of various PG receptors in the trabecular meshwork increases outflow through the expression of TNF-α. There are multiple mechanisms for increased uveoscleral outflow. Action on specific PG receptors leads to remodeling of the extracellular matrix, and increased secretion of metalloproteinases, which reduces resistance to aqueous outflow.
Fig. 1 Mechanism of action of prostaglandins. (Piplani P, et al., 2016)
Currently available prostaglandin analogs include FP receptor analogs with high affinity for FP receptors, EP receptor analogs with the highest number of binding sites, and DP receptor analogs that target DP receptors in the ciliary muscle.
Solutions of Prostaglandin Analog Development for Glaucoma
For the treatment of glaucoma, the family of compounds known as PG derivatives needs to be further explored. Whether targeting the FP receptor, the EP receptor, or the DP receptor, we are committed to providing offer an increasing number of studies to advance the development of PG analogs as potent drugs with safety and efficacy.
Table 1. Our specific solutions for prostaglandin analogs for glaucoma.
| Development Strategies | Our Solutions |
|---|---|
| Prostanoid FP agonists | FP receptors are found in the ciliary muscle, ciliary epithelium, and trabecular meshwork and iris stromal tissue. Our solution is to develop agonists with high affinity for FP receptors or novel agonists with a dual mechanism of action to promote aqueous efflux and increase the available options for glaucoma treatment. Design prostaglandin analogs that are synthesized as ester prodrugs to enhance transmembrane permeability and are hydrolyzed to acids at the membrane to display the desired effect. |
| Prostanoid EP agonists | EP receptors are widely expressed in the human anterior chamber. We target multiple EP receptors such as EP1, EP2, EP3 and EP4 and design PGE derivatives to replace different sites of carboxyl groups to optimize the selectivity and potency for EP receptors. |
| Prostanoid DP agonists | DP receptors have been less studied. We offer the development of PGD series derivatives to improve the binding affinity and functional activity for DP receptors by substituting carboxylic acid groups. |
Our Highlights
- A new generation of compounds with multiple mechanisms of action is being vigorously investigated in the laboratory.
- New PG receptor agonists with dual mechanisms of action add to the options available for glaucoma treatment.
- We are committed to providing innovative formulations with high efficiency and less adverse effects.
We hope that our service to find new molecular drugs for glaucoma will become an available avenue for future glaucoma treatment.
Reference
- Piplani P, et al. Prostaglandin analogues: current treatment option for glaucoma. Med Chem Res, 2016, 25, 1031–1048.