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

Award Number: SC2GM135020
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$25,981 )
2024	2022	CSU FULLERTON AUXILIARY SERVICES CORPORATION	1121 N STATE COLLEGE BLVD	FULLERTON	CA	92831	ORANGE	USA	Biomedical Research and Research Training	000	3	12/5/2023	NON-COMPETING CONTINUATION	-$25,981
														Subtotal = -$25,981

Issue Date FY: 2022 ( Subtotal = $142,000 )
2022	2022	CSU FULLERTON AUXILIARY SERVICES CORPORATION	1121 NORTH STATE COLLEGE BOULEVARD	FULLERTON	CA	92831	ORANGE	USA	Biomedical Research and Research Training	000	3	5/12/2022	NON-COMPETING CONTINUATION	$142,000
														Subtotal = $142,000

Issue Date FY: 2021 ( Subtotal = $142,000 )
2021	2021	CSU FULLERTON AUXILIARY SERVICES CORPORATION	1121 NORTH STATE COLLEGE BOULEVARD	FULLERTON	CA	92831	ORANGE	USA	Biomedical Research and Research Training	000	2	4/16/2021	NON-COMPETING CONTINUATION	$142,000
														Subtotal = $142,000

Issue Date FY: 2020 ( Subtotal = $142,000 )
2020	2020	CSU FULLERTON AUXILIARY SERVICES CORPORATION	1121 NORTH STATE COLLEGE BOULEVARD	FULLERTON	CA	92831	ORANGE	USA	Biomedical Research and Research Training	000	1	4/29/2020	NEW	$142,000
														Subtotal = $142,000

Grand Total All Awards = $400,019

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

Award Number: SC2GM135020

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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