Chronic pain is a debilitating health condition that is currently insufficiently treated by available therapies. Ther is a growing need to develop alternatives to treat chronic pain and specifically diabetic neuropathy as diabetes is increasing worldwide and painful neuropathy occurs in 50% of diabetic patients. Recently, the importance of lipids as signaling mediators and their functional significance in nociception has been elucidated. Epoxy-fatty acid metabolites generated by cytochrome P450s mediate analgesia, and we have synthesized small molecule inhibitors of their metabolizing enzyme, the soluble epoxide hydrolase (sEH), to elevate their levels in vivo. With this proposal, we aim to develop a novel and safe oral inhibitor of sEH for the treatment of peripheral neuropathy in diabetic patients. Preclinical studies with our candidate, EC5026, demonstrate efficacy that exceeds current therapies for diabetic neuropathy. Based on efficacy, good PK/ADME properties and stability, EicOsis has selected EC5026 to enter further development stages. EicOsis will work with Blueprint Development Teams to create a development plan and initiate studies to test the safety of EC5026 in Phase 1 clinical trials.
Chronic pain is a worldwide health concern insufficiently treated by currently available therapies; and specifically diabetic neuropathy is a growing problem as the population of diabetic patients increases. EicOsis has identified a first in class small molecule inhibitor of the soluble epoxide hydrolase enzyme, a key regulator of analgesic lipid metabolites, with high efficacy, good PK/ADME properties and stability to enter further development stages. EicOsis will work with Blueprint Development Teams to create a development plan and initiate studies to test the safety of EC5026 in Phase 1 clinical trials.
| 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 |
| Wagner, K; Lee, K S S; Yang, J et al. (2017) Epoxy fatty acids mediate analgesia in murine diabetic neuropathy. Eur J Pain 21:456-465 |
