# Development of dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors as a Promising Therapeutic Strategy for the Treatment of Acute and Chronic Pain

> **NIH NIH SC2** · CALIFORNIA STATE UNIVERSITY FULLERTON · 2020 · $142,000

## Abstract

Project Summary/Abstract
 We aim to develop dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors that will be used
as a promising novel therapeutic strategy in the pain management. We will study a series of benzothiazole-
phenyl piperidine analogs which exhibit potent inhibition at both targeted enzymes, and that are metabolically
stable in liver microsomes. The compounds we propose to study represent a much-needed, completely novel,
nonopioid, starting point in pain management research. Because this class has different biological targets from
existing analgesics, it represents an opportunity to solve long-standing problems that have been linked to the
existing therapies in pain management. In this project we propose that the simultaneous regulation of the two
enzymes, soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH), by dual inhibitors, can be
expected to play a significant role in the success of this therapeutic strategy. We know that co-administration of
sEH and FAAH inhibitors significantly reduces pain in several animal models of pain. However, this promising
strategy of dual inhibitors of both enzymes has not been robustly investigated as a nonopioid pain medication
development approach. This novel class of nonopioid analgesics provides flexibility and an advance in the
medicinal chemistry space that may overcome weaknesses in the currently available pain treatments. The most
original and mechanistically distinct aspect of these compounds is their ability to simultaneously inhibit two
different enzymes that play significant roles in pain and inflammation. Overall, the combination of structure-
activity relationship studies and computational approaches in this proposal will enable a detailed characterization
of the molecular determinants required for dual inhibition of these novel ligands. This will ultimately allow the
development of potent and metabolically stable dual sEH/FAAH inhibitors. Such molecules will be valuable to
study as pain management therapeutics with predictably superior clinical profiles as compared to current opioid
and nonopioid drugs.

## Key facts

- **NIH application ID:** 9852908
- **Project number:** 1SC2GM135020-01
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY FULLERTON
- **Principal Investigator:** Stevan Pecic
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $142,000
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852908

## Citation

> US National Institutes of Health, RePORTER application 9852908, Development of dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors as a Promising Therapeutic Strategy for the Treatment of Acute and Chronic Pain (1SC2GM135020-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9852908. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*