Pain is a serious health problem affecting a large proportion of the general population. The burden of painful conditions on the individuals and the society follow a rising trajectory because of the paucity of effective and reasonably safe pharmaceuticals that are needed globally. Aging population and diabetes epidemic are two key factors that drive the number of people that will need efficacious analgesics. More than 75% of the analgesic market in volume is dominated by cyclooxygenase inhibitors. However lack of efficacy in neuropathic pain and side effects limit their use. Other approved therapeutics also suffers from lack of efficacy and diverse and serious side effects. This underlines the need to discover novel therapeutic agents to alleviate pain. In order to meet this need, Eicosis'overall objective is the development of a novel promising class of orally active analgesic drug that targets the soluble epoxide hydrolase (sEH), a new therapeutic target for pain. The inhibitors of sEH are not only more efficacious than COX inhibitors on inflammatory pain, but also they block intractable neuropathic pain more efficaciously than commercial standards gabapentin and pregabalin without the motor side effects. In this proposal, Eicosis will identify and select an IN candidate and a back-up compound for the treatment of painful conditions.
Pain is a major health problem. Although a number of treatment options exist, most patients suffer from unfavorable side effects and limited efficacy. The lead compounds developed in this proposal have the potential to overcome these problems and deliver a novel solution to effectively treat chronic and neuropathic pain.
Napimoga, M H; Rocha, E P; Trindade-da-Silva, C A et al. (2018) Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption. J Periodontal Res 53:743-749 |
Trindade-da-Silva, Carlos Antonio; Bettaieb, Ahmed; Napimoga, Marcelo Henrique et al. (2017) Soluble Epoxide Hydrolase Pharmacological Inhibition Decreases Alveolar Bone Loss by Modulating Host Inflammatory Response, RANK-Related Signaling, Endoplasmic Reticulum Stress, and Apoptosis. J Pharmacol Exp Ther 361:408-416 |
Wagner, Karen M; McReynolds, Cindy B; Schmidt, William K et al. (2017) Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases. Pharmacol Ther 180:62-76 |
Inceoglu, Bora; Bettaieb, Ahmed; Trindade da Silva, Carlos A et al. (2015) Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain. Proc Natl Acad Sci U S A 112:9082-7 |