Last update 01 Nov 2024

FAAH2

Last update 01 Nov 2024

Basic Info

Synonyms

AMDD, amidase domain containing, Amidase domain-containing protein

+ [8]

Introduction

Catalyzes the hydrolysis of endogenous amidated lipids like the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides, to their corresponding fatty acids, thereby regulating the signaling functions of these molecules (PubMed:17015445, PubMed:19926788). Hydrolyzes monounsaturated substrate anandamide preferentially as compared to polyunsaturated substrates.

Drugs associated with FAAH2

Redafamdastat

Target

FAAH2

Mechanism

FAAH2 inhibitors

Active Org.

Jazz Pharmaceuticals Plc [+1]

Originator Org.

Pfizer Inc.

Active Indication

Stress Disorders, Post-Traumatic

Inactive Indication

Acute Pain [+4]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

URB-597

Target

FAAH2

Mechanism

FAAH2 inhibitors

Active Org.

Kadmus Pharmaceuticals, Inc. [+1]

Originator Org.

Kadmus Pharmaceuticals, Inc.

Active Indication

Schizophrenia

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ARN-2508

Target

COX-1 x COX-2 x FAAH2

Mechanism

COX-1 inhibitors [+2]

Active Org.

University of California, Irvine Extension

Originator Org.

University of California, Irvine Extension

Active Indication

Inflammation [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with FAAH2

NCT05178316 / CompletedPhase 2

A Multicenter Phase 2, 12-week Double-blind, Placebo-controlled, Randomized, Parallel-group Study of JZP150 for the Treatment of Posttraumatic Stress Disorder

This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter study of the safety and efficacy of JZP150 in the treatment of adult participants with post-traumatic stress disorder (PTSD).

Start Date29 Dec 2021

Sponsor / Collaborator

Jazz Pharmaceuticals, Inc.

NCT00916201 / Unknown statusPhase 1IIT

Evaluation of Potential Central Glucoregulatory Compounds to Treat/Ameliorate the Symptoms of Schizophrenia: a Proof-of-concept Study in Healthy Volunteers.

Different compounds that might modify the glucose regulation in the central nervous system will be evaluated in healthy volunteers. Several examinations will be performed in order to get a detailed plan how these substances might work.

Start Date01 Jun 2020

Sponsor / Collaborator

Zentralinstitut für Seelische Gesundheit

[+1]

NCT03386487 / CompletedPhase 2IIT

A Phase 2B, 8-week, Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate Efficacy, Safety and Tolerability of the Fatty Acid Amide Hydrolase (FAAH) Inhibitor PF-04457845 in Adults With DSM5 Current Cannabis Use Disorder (CUD)

A Phase 2B, 8-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety and Tolerability of the Fatty Acid Amide Hydrolase (FAAH) Inhibitor PF-04457845 in Adults with DSM-5 Current Cannabis Use Disorder (CUD)

Start Date14 Jan 2019

Sponsor / Collaborator

Yale University

[+4]

100 Clinical Results associated with FAAH2

100 Translational Medicine associated with FAAH2

0 Patents (Medical) associated with FAAH2

Literatures (Medical) associated with FAAH2

01 Nov 2024·Neurochemical Research

Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana

Article

Author: Burrell, Brian D ; Paulsen, Riley T ; Kabeiseman, Emily

AbstractThe endocannabinoid system plays a critical role in modulating both peripheral and central nervous system function. Despite being present throughout the animal kingdom, there has been relatively little investigation of the endocannabinoid system beyond traditional animal models. In this study, we report on the identification and characterization of a putative fatty acid amide hydrolase (FAAH) in the medicinal leech, Hirudo verbana. FAAH is the primary enzyme responsible for metabolizing the endocannabinoid signaling molecule arachidonoyl ethanolamide (anandamide or AEA) and therefore plays a critical role in regulating AEA levels in the nervous system. mRNA encoding Hirudo FAAH (HirFAAH) is expressed in the leech central nervous system (CNS) and sequence analysis suggests that this is an orthologue of FAAH-2 observed in vertebrates. Functionally, HirFAAH has serine hydrolase activity based on activity-based protein profiling (ABPP) studies using the fluorophosphonate probe TAMRA-FP. HirFAAH also hydrolyzes arachidonyl 7-amino, 4-methyl coumarin amide (AAMCA), a substrate specific to FAAH. Hydrolase activity during both the ABPP and AAMCA assays was eliminated by a mutation at a conserved catalytic serine. Activity was also blocked by the known FAAH inhibitor, URB597. Treatment of Hirudo ganglia with URB597 potentiated synapses made by the pressure-sensitive mechanosensory neuron (P cell), mimicking the effects of exogenously applied AEA. The Hirudo CNS has been a useful system in which to study properties of endocannabinoid modulation of nociception relevant to vertebrates. Therefore, this characterization of HirFAAH is an important contribution to comparative studies of the endocannabinoid system.

26 Jul 2023·Scientific reports

N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model.

Article

Author: Morin, Sophie ; Rioux, Geneviève ; Pouliot, Roxane ; Flamand, Nicolas ; Tremblay, Andréa ; Simard, Mélissa

Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation and dysregulated lipid metabolism. Some lipid mediators of the N-acylethanolamines (NAEs) and monoacylglycerols (MAGs) can bind to cannabinoid (CB) receptors and are referred to as part of the endocannabinoidome. Their implication in psoriasis remains unknown. The aim of the present study was to characterize the endocannabinoid system and evaluate the effects of n-3-derived NAEs, namely N-eicosapentaenoyl-ethanolamine (EPEA), in psoriatic keratinocytes using a psoriatic skin model produced by tissue engineering, following the self-assembly method. Psoriatic skin substitutes had lower FAAH2 expression and higher MAGL, ABHD6 and ABHD12 expression compared with healthy skin substitutes. Treatments with alpha-linolenic acid (ALA) increased the levels of EPEA and 1/2-docosapentaenoyl-glycerol, showing that levels of n-3 polyunsaturated fatty acids modulate related NAE and MAG levels. Treatments of the psoriatic substitutes with 10 μM of EPEA for 7 days resulted in decreased epidermal thickness and number of Ki67 positive keratinocytes, both indicating decreased proliferation of psoriatic keratinocytes. EPEA effects on keratinocyte proliferation were inhibited by the CB₁ receptor antagonist rimonabant. Exogenous EPEA also diminished some inflammatory features of psoriasis. In summary, n-3-derived NAEs can reduce the psoriatic phenotype of a reconstructed psoriatic skin model.

01 Jun 2023·American journal of medical genetics. Part A

Clinical exome sequencing findings in 1589 patients.

Article

Author: Gorukmez, Ozlem ; Gorukmez, Orhan ; Topak, Ali

Clinical exome sequencing (CES) is important for the diagnosis of Mendelian diseases, which are clinically and etiologically heterogeneous. Sharing of large amounts of CES data associated with clinical findings will increase the accuracy of variant interpretation. We performed a retrospective study to state the diagnostic yield of CES in 1589 patients with a wide phenotypic spectrum. CES was performed using the Sophia Clinical Exome Sequencing Kit with 4493 genes, followed by sequencing on a NextSeq 500 system. The diagnosis rate was 36.8% when only pathogenic and likely pathogenic variants were included. Consanguineous unions and positive family history were associated with a high diagnostic yield. The neurological disease group had the highest number of patients. The groups with high diagnosis rates were ear, eye, and muscle disease groups. Seven candidate genes (EFHC2, HSPB3, FAAH2, ITGB1, GYG2, CD177, and CSTF2T) that are not yet associated with human diseases were identified. Owing to the high diagnostic yield of CES compared with that of other genetic tests, it can be used as a standard diagnostic test in patients with rare genetic disorders that require a wide differential diagnosis, especially in laboratories with limited resources.

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FAAH2

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