更新于：2024-09-19

FAAH2

更新于：2024-09-19

基本信息

别名

AMDD、amidase domain containing、Amidase domain-containing protein

+ [8]

简介

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.

关联

项与 FAAH2 相关的药物

JNJ-42165279

靶点

FAAH2

作用机制

FAAH2抑制剂

在研机构

Janssen Research & Development LLC

原研机构

Janssen Global Services LLC

在研适应症

自闭症谱系障碍

非在研适应症

焦虑 [+4]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Redafamdastat

靶点

FAAH2

作用机制

FAAH2抑制剂

在研机构

Jazz Pharmaceuticals Plc [+1]

原研机构

Pfizer Inc.

在研适应症

创伤后应激障碍

非在研适应症

急性疼痛 [+4]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

URB-597

靶点

FAAH2

作用机制

FAAH2抑制剂

在研机构

Kadmus Pharmaceuticals, Inc. [+1]

原研机构

Kadmus Pharmaceuticals, Inc.

在研适应症

精神分裂症

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 FAAH2 相关的临床试验

NCT05178316 / Completed临床2期

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).

开始日期2021-12-29

申办/合作机构

Jazz Pharmaceuticals, Inc.

NCT00916201 / Unknown status临床1期

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.

开始日期2020-06-01

申办/合作机构

Zentralinstitut für Seelische Gesundheit

[+1]

NCT03386487 / Completed临床2期IIT

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)

开始日期2019-01-14

申办/合作机构

Yale University

[+4]

100 项与 FAAH2 相关的临床结果

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100 项与 FAAH2 相关的转化医学

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0 项与 FAAH2 相关的专利（医药）

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项与 FAAH2 相关的文献（医药）

2023-07-26·Scientific reports

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

Article

作者: 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.

2023-06-01·American journal of medical genetics. Part A

Clinical exome sequencing findings in 1589 patients.

Article

作者: 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.

2023-05-09·Scientific reports

Two legume fatty acid amide hydrolase isoforms with distinct preferences for microbial- and plant-derived acylamides

Article

作者: Herrell, Emily ; Chapman, Kent D. ; Aziz, Mina ; Arias-Gaguancela, Omar

Fatty acid amide hydrolase (FAAH) is a widely conserved amidase in eukaryotes, perhaps best known for inactivating N-acylethanolamine lipid mediators. However, FAAH enzymes hydrolyze a wide range of acylamide substrates. Analysis of FAAHs from multiple angiosperm species revealed two conserved phylogenetic groups that differed in key conserved residues in the substrate binding pocket. While the foundation group of plant FAAHs, designated FAAH1, has been studied at the structural and functional level in Arabidopsis thaliana, nothing is known about FAAH2 members. Here, we combined computational and biochemical approaches to compare the structural and enzymatic properties of two FAAH isoforms in the legume Medicago truncatula designated MtFAAH1 and MtFAAH2a. Differences in structural and physicochemical properties of the substrate binding pockets, predicted from homology modeling, molecular docking, and molecular dynamic simulation experiments, suggested that these two FAAH isoforms would exhibit differences in their amidohydrolase activity profiles. Indeed, kinetic studies of purified, recombinant MtFAAHs indicated a reciprocal preference for acylamide substrates with MtFAAH1 more efficiently utilizing long-chain acylamides, and MtFAAH2a more efficiently hydrolyzing short-chain and aromatic acylamides. This first report of the enzymatic behavior of two phylogenetically distinct plant FAAHs will provide a foundation for further investigations regarding FAAH isoforms in legumes and other plant species.