FAAH

Summary

FAAH (fatty acid amide hydrolase, HGNC:3553) is a protein-coding gene on chromosome 1p33, encoding Fatty-acid amide hydrolase 1 (O00519). 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 regul….

This gene encodes a protein that is responsible for the hydrolysis of a number of primary and secondary fatty acid amides, including the neuromodulatory compounds anandamide and oleamide.

Source: NCBI Gene 2166 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 102 total — 1 likely-pathogenic
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3553
Approved symbol	FAAH
Name	fatty acid amide hydrolase
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	FAAH-1, FAAH1
Ensembl gene	ENSG00000117480
Ensembl biotype	protein_coding
OMIM	602935
Entrez	2166

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 26 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000243167, ENST00000468718, ENST00000484697, ENST00000489366, ENST00000493636, ENST00000493735, ENST00000877141, ENST00000877142, ENST00000877143, ENST00000877144, ENST00000877145, ENST00000877146, ENST00000877147, ENST00000877148, ENST00000877149, ENST00000877150, ENST00000877151, ENST00000877152, ENST00000877153, ENST00000877154, ENST00000877155, ENST00000877156, ENST00000877157, ENST00000877158, ENST00000936570, ENST00000936571, ENST00000936572, ENST00000936573, ENST00000936574, ENST00000936575, ENST00000952350

RefSeq mRNA: 1 — MANE Select: NM_001441 NM_001441

CCDS: CCDS535

Canonical transcript exons

ENST00000243167 — 15 exons

Exon	Start	End
ENSE00001524579	46394317	46394543
ENSE00001624215	46413075	46413220
ENSE00001671848	46405588	46405794
ENSE00001819666	46413447	46413845
ENSE00003477195	46412143	46412251
ENSE00003489051	46410814	46410854
ENSE00003516265	46406244	46406368
ENSE00003517557	46408459	46408584
ENSE00003602638	46405014	46405148
ENSE00003602910	46402091	46402204
ENSE00003612601	46410398	46410497
ENSE00003656039	46411612	46411651
ENSE00003666684	46406038	46406078
ENSE00003669260	46409101	46409198
ENSE00003693215	46405372	46405505

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 97.98.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8009 / max 198.2184, expressed in 833 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2741	6.7181	832
2740	0.0828	38

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	97.98	gold quality
left lobe of thyroid gland	UBERON:0001120	97.54	gold quality
mucosa of transverse colon	UBERON:0004991	96.93	gold quality
thyroid gland	UBERON:0002046	96.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.68	gold quality
left testis	UBERON:0004533	95.65	gold quality
right testis	UBERON:0004534	95.44	gold quality
cerebellar hemisphere	UBERON:0002245	95.26	gold quality
cerebellar cortex	UBERON:0002129	95.13	gold quality
right lobe of liver	UBERON:0001114	95.07	gold quality
spinal cord	UBERON:0002240	94.46	gold quality
nucleus accumbens	UBERON:0001882	94.44	gold quality
body of pancreas	UBERON:0001150	94.42	gold quality
metanephros cortex	UBERON:0010533	94.18	gold quality
right frontal lobe	UBERON:0002810	93.92	gold quality
right uterine tube	UBERON:0001302	93.76	gold quality
cerebellum	UBERON:0002037	93.54	gold quality
testis	UBERON:0000473	93.44	gold quality
transverse colon	UBERON:0001157	93.05	gold quality
middle frontal gyrus	UBERON:0002702	92.85	gold quality
pituitary gland	UBERON:0000007	92.82	gold quality
minor salivary gland	UBERON:0001830	92.81	gold quality
right adrenal gland cortex	UBERON:0035827	92.80	gold quality
adenohypophysis	UBERON:0002196	92.79	gold quality
rectum	UBERON:0001052	92.40	gold quality
right adrenal gland	UBERON:0001233	92.36	gold quality
putamen	UBERON:0001874	92.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.31	gold quality
prostate gland	UBERON:0002367	92.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	188.31
E-ANND-3	yes	5.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IKZF1, MBD2, STAT3

miRNA regulators (miRDB)

27 targeting FAAH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-943	97.81	64.42	694
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-7976	95.75	65.67	1186

Literature-anchored findings (GeneRIF, showing 40)

• Low levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer. (PMID:11818522)
• Fatty acid amide hydrolase in human central nervous system is found in both neuronal and glial elements and shows a significant overlap with central cannabinoid receptors. (PMID:12008024)
• missense mutation associcated with problem drug use (PMID:12060782)
• dendritic cells were also found to express measurable amounts of CB1 and CB2 receptors and of FAAH. Cell maturation did not consistently modify the expression of these proteins (PMID:12153574)
• Leptin actives the promoter of this enzyme in T cells through STAT3. (PMID:12556536)
• fatty acid amide hydrolase (FAAH) promoter is activated by progesterone in human T lymphocytes through the transcription factor Ikaros (PMID:12799380)
• In hippocampus and entorhinal cortex of Alzheimer’s disease patients both fatty acid amide hydrolase and cannabinoid CB2 receptors are abundantly and selectively expressed in neuritic plaque-associated astrocytes and microglia (PMID:14657172)
• This review discusses the participation of anandamide (AEA) in hormone-cytokine networks that are essential for human reproduction and the key role played by anandamide hydrolase (FAAH) in regulating the activity of AEA. (PMID:15219977)
• The natural 385A SNP in the human FAAH gene produces a mutant enzyme with reduced cellular stability, thus fortifying a potential link between functional abnormalities in the endocannabinoid system and drug abuse and dependence. (PMID:15254019)
• P129T mutation is the only common mutation in the FAAH gene and is significantly associated with addictive traits (PMID:16972078)
• FAAH gene expression was negatively correlated with visceral fat mass and circulating 2-arachidonylglycerol. (PMID:17065342)
• study was unable to find robust evidence of an association of the Pro129Thr FAAH variant with overweight, obesity, and any related quantitative traits among the examined whites (PMID:17216208)
• The relationship between the FAAH A/A genotype and risk for drug dependence in this study was drug class specific, suggesting it is not part of a more general drug abuse effect (PMID:17290447)
• finding reported in this study is that lymphocytes of Huntington’s disease patients show a dramatic decrease in FAAH activity (PMID:17553686)
• not associated with susceptibility to alcoholism in a Japanese population. (PMID:17621164)
• The endocannabinoid system is activated in obese visceral adipose tissue as shown by decreased FAAH, Cb1, and adiponectin expression. (PMID:17712725)
• FAAH genotype was associated with symptom phenotype and faster colonic transit in functional gastrointestinal disorders. (PMID:17962356)
• faah is induced in beta-amyloid plaque-associated microglia and astroglia, respectively, in Down’s syndrome (PMID:18068305)
• This study found significant over-representations of the FAAH 385 A allele in overweight/obese subjects and presents new data in binge eating disorder (BED) patients that the 385 mutation is not significantly associated with BED-related obesity. (PMID:18295974)
• An FAAH defective gene variant results in lower BP in young males, but this effect is lost in older obese hypertensive patients (PMID:18497731)
• fatty acid amide hydrolase is potentially involved in prostate tumorigenesis. (PMID:18566995)
• The CNR1 SNP displayed a significant abstinence x genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence x genotype interaction on craving. (PMID:18705688)
• FAAH appears to be over expressed in trophoblasts that have invaded the decidua, as well as in large decidual stromal cells in many cases of recurrent miscarriage (PMID:18805581)
• We were unable to find robust evidence of an association of the Pro129Thr variant of FAAH with severe obesity (PMID:18819056)
• Biochemical and biological properties of 4-(3-phenyl-[1,2,4] thiadiazol-5-yl)-piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty acid amide hydrolase. (PMID:19095868)
• The C385A carriers of Fatty acid amide hydrolase showed decreased correlation between amygdala reactivity and trait anxiety but increased correlation between ventral striatal reactivity and delay discounting, an index of impulsivity. (PMID:19103437)
• There is no evidence for an association of common variants in the CNR1 and FAAH genes with measures of adiposity. (PMID:19165169)
• Very low or absent FAAH and high CB1 levels correspond with spontaneous miscarriage. (PMID:19419760)
• Individuals with single nucleotide gene polymorphisms at rs3766246 and rs2295633 in the fatty-acid hydrolase gene have significantly higher arousal ratings following amphetatime administration. (PMID:19890266)
• Genetic variability in FAAH is associated with dyslipidemia, independent of insulin response. (PMID:19958092)
• The underlying mechanism of these genetic effects may be enhanced neural response in reward areas of the brain in carriers of the CNR1 G allele and FAAH C/C genotype in response to marijuana cues. (PMID:20010552)
• The levels of the CB1 receptors and the fatty acid amide hydrolase were significantly lower in the ventral striatum of CA compared to the control group. (PMID:20015515)
• The combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (PMID:20044928)
• results in 5,109 subjects suggest that fatty acid amide hydrolase(FAAH) Pro129Thr polymorphism may modestly contribute to class III adult obesity in the French population (PMID:20054193)
• There is an association of the mutant type group A358C and A358A of FAAH with a worse cardiovascular profile (weight, body mass index, waist circumference, insulin,TNF-alpha and adiponectin levels) than wild type group. (PMID:20056290)
• The novel finding is the association of the mutant type group A358C of FAAH with lower glucose, insulin and insulin sensitivity levels than of the wild-type group with higher visfatin levels. (PMID:20065978)
• These findings, although preliminary, suggest that the FAAH cDNA gene variants may contribute to the susceptibility to mood disorders (PMID:20080186)
• FAAH expression and hydrolysis activity in the colon decrease in children with slow transit constipation. (PMID:20099163)
• The allele A358 of fatty acid amide hydrolase was associated with a lack of improvement on glucose insulin, HOMA, and leptin levels after weight loss. (PMID:20102775)
• In patients with morbid obesity, the C358A polymorphism of FAAH was not associated with anthropometric parameters, biochemical markers or adipocytokine levels. (PMID:20189896)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Faah	ENSMUSG00000034171
rattus_norvegicus	Faah	ENSRNOG00000045949
drosophila_melanogaster	CG7910	FBGN0037547
drosophila_melanogaster	CG7900	FBGN0037548
caenorhabditis_elegans		WBGENE00012750
caenorhabditis_elegans		WBGENE00013226
caenorhabditis_elegans		WBGENE00013232
caenorhabditis_elegans		WBGENE00015047
caenorhabditis_elegans		WBGENE00015048

Paralogs (2): QRSL1 (ENSG00000130348), FAAH2 (ENSG00000165591)

Protein

Protein identifiers

Fatty-acid amide hydrolase 1 — O00519 (reviewed: O00519)

Alternative names: Anandamide amidohydrolase 1, Fatty acid ester hydrolase, Oleamide hydrolase 1

All UniProt accessions (2): A0A087WYA0, O00519

UniProt curated annotations — full annotation on UniProt →

Function. 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. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates. It can also catalyze the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol). FAAH cooperates with PM20D1 in the hydrolysis of amino acid-conjugated fatty acids such as N-fatty acyl glycine and N-fatty acyl-L-serine, thereby acting as a physiological regulator of specific subsets of intracellular, but not of extracellular, N-fatty acyl amino acids.

Subunit / interactions. Homodimer.

Subcellular location. Endomembrane system. Cytoplasm. Cytoskeleton.

Tissue specificity. Highly expressed in the brain, small intestine, pancreas, skeletal muscle and testis. Also expressed in the kidney, liver, lung, placenta and prostate.

Activity regulation. Inhibited by O-aryl carbamates and alpha-keto heterocycles. Inhibited by trifluoromethyl ketone.

Polymorphism. Genetic variations in FAAH can be associated with susceptibility to polysubstance abuse [MIM:606581]. At homozygosity, variant Thr-129 is strongly associated with drug and alcohol abuse, and methamphetamine dependence.

Similarity. Belongs to the amidase family.

RefSeq proteins (1): NP_001432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020556	Amidase_CS	Conserved_site
IPR023631	Amidase_dom	Domain
IPR036928	AS_sf	Homologous_superfamily
IPR052096	Endocannabinoid_amidase	Family

Pfam: PF01425

Enzyme classification (BRENDA):

• EC 3.5.1.4 — amidase (BRENDA: 67 organisms, 400 substrates, 635 inhibitors, 203 Km, 135 kcat entries)
• EC 3.5.1.99 — fatty acid amide hydrolase (BRENDA: 10 organisms, 176 substrates, 1033 inhibitors, 73 Km, 48 kcat entries)

Substrate kinetics (BRENDA)

120 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETAMIDE	0.27–100	25
PROPIONAMIDE	0.0001–88	18
BENZAMIDE	0.0007–7.25	17
ACRYLAMIDE	1.2–93	16
OLEAMIDE	0.007–0.037	11
ISOBUTYRAMIDE	0.0001–7	10
BUTYRAMIDE	0.1–14	7
OLEOYL P-NITROANILIDE	0.012–0.126	7
NICOTINAMIDE	0.3–135.6	6
HEXANAMIDE	0.3–11.08	5
ANANDAMIDE	0.0018–2.78	5
MYRISTOYL P-NITROANILIDE	0.069–0.099	5
NONANOYL P-NITROANILIDE	0.057–0.57	5
2-TOLUAMIDE	0.1–0.3	4
CYCLOMALTOHEXAOSE	0.2–0.3	4

Catalyzed reactions (Rhea), 12 shown:

• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:26132)
• N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate (RHEA:26136)
• (9Z)-octadecenamide + H2O = (9Z)-octadecenoate + NH4(+) (RHEA:26506)
• N-(9Z-hexadecenoyl) ethanolamine + H2O = (9Z)-hexadecenoate + ethanolamine (RHEA:35563)
• N-(9Z-octadecenoyl) ethanolamine + H2O = ethanolamine + (9Z)-octadecenoate (RHEA:45060)
• N-hexadecanoylethanolamine + H2O = ethanolamine + hexadecanoate (RHEA:45064)
• (9Z)-octadecenoate + glycine = N-(9Z-octadecenoyl)glycine + H2O (RHEA:51316)
• (9Z,12Z,15Z)-octadecatrienamide + H2O = (9Z,12Z,15Z)-octadecatrienoate + NH4(+) (RHEA:62976)
• hexadecanamide + H2O = hexadecanoate + NH4(+) (RHEA:62984)
• tetradecamide + H2O = tetradecanoate + NH4(+) (RHEA:62992)
• (8Z,11Z,14Z)-eicosatrienamide + H2O = (8Z,11Z,14Z)-eicosatrienoate + NH4(+) (RHEA:62996)
• (11Z,14Z,17Z)-eicosatrienamide + H2O = (11Z,14Z,17Z)-eicosatrienoate + NH4(+) (RHEA:63000)

UniProt features (15 total): binding site 3, active site 3, sequence variant 2, topological domain 2, chain 1, transmembrane region 1, modified residue 1, sequence conflict 1, intramembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00519-F1	95.44	0.93

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 142 (charge relay system); 217 (charge relay system); 241 (acyl-ester intermediate)

Ligand- & substrate-binding residues (3): 238–241; 191; 217

Post-translational modifications (1): 241

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2142753	Arachidonate metabolism

MSigDB gene sets: 184 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_ETHANOL, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_VASOCONSTRICTION, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN

GO Biological Process (8): fatty acid catabolic process (GO:0009062), arachidonate metabolic process (GO:0019369), positive regulation of vasoconstriction (GO:0045907), monoacylglycerol catabolic process (GO:0052651), regulation of trans-synaptic signaling by endocannabinoid, modulating synaptic transmission (GO:0150036), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), lipid catabolic process (GO:0016042)

GO Molecular Function (9): amidase activity (GO:0004040), phospholipid binding (GO:0005543), fatty acid amide hydrolase activity (GO:0017064), identical protein binding (GO:0042802), monoacylglycerol lipase activity (GO:0047372), protein binding (GO:0005515), lipid binding (GO:0008289), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788)

GO Cellular Component (9): endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), organelle membrane (GO:0031090), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fatty acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
synapse	3
lipid metabolic process	2
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	2
binding	2
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
long-chain fatty acid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of multicellular organismal process	1
monoacylglycerol metabolic process	1
acylglycerol catabolic process	1
modulation of chemical synaptic transmission	1
trans-synaptic signaling by endocannabinoid, modulating synaptic transmission	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
catabolic process	1
lipid binding	1
protein binding	1
lipase activity	1
carboxylic ester hydrolase activity	1
catalytic activity	1
hydrolase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
membrane	1
membrane-bounded organelle	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

2408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAAH	MGLL	Q99685	973
FAAH	CNR1	P21554	972
FAAH	NAPEPLD	Q6IQ20	925
FAAH	DAGLA	Q9Y4D2	895
FAAH	FABP5	Q01469	891
FAAH	CNR2	P34972	887
FAAH	ABHD6	Q9BV23	882
FAAH	TRPV1	Q8NER1	854
FAAH	NAAA	Q02083	848
FAAH	DAGLB	Q8NCG7	848
FAAH	GPR55	Q9Y2T6	848
FAAH	FABP7	O15540	839
FAAH	FABP3	P05413	826
FAAH	ABHD12	Q8N2K0	823
FAAH	GPR18	Q14330	736

IntAct

26 interactions, top by confidence:

A	B	Type	Score
FAAH	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	FAAH	psi-mi:“MI:0915”(physical association)	0.560
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
CXCR2	FAAH	psi-mi:“MI:0915”(physical association)	0.400
MME		psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
PIGH	ILVBL	psi-mi:“MI:0914”(association)	0.350
TTMP	NBAS	psi-mi:“MI:0914”(association)	0.350
CYP19A1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	FAAH	psi-mi:“MI:0914”(association)	0.350
MFSD5	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC38A8	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A6	FAAH	psi-mi:“MI:0914”(association)	0.350
TMEM241	FAAH	psi-mi:“MI:0914”(association)	0.350
FAAH	dinB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): NOTCH2NL (Two-hybrid), FAAH (Affinity Capture-MS), FAAH (Proximity Label-MS), FAAH (Proximity Label-MS), FAAH (Proximity Label-MS), FAAH (Proximity Label-MS), FAAH (Proximity Label-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS), FAAH (Affinity Capture-MS)

ESM2 similar proteins: A5GFZ6, A7MBC0, A7MBI7, D4AAT7, E1BNQ4, E2QUI9, F1Q575, O00519, O08914, O95396, P13439, P17256, P19971, P31754, P51175, Q03426, Q0VGK3, Q2KJF7, Q5BJY6, Q5E9T8, Q5FVR2, Q5I0L3, Q5R514, Q5R7A2, Q5R824, Q5XIG6, Q641W2, Q6DH69, Q86U10, Q8BYL4, Q8CIM3, Q8IVS8, Q8IW45, Q8JZV7, Q8K4F5, Q8NFV4, Q8QZY2, Q91X91, Q91YR5, Q921Q3

Diamond homologs: A0A348AXX5, A0KBH9, A0L5G0, A0LSR0, A1V776, A1WVR7, A2S8I9, A3MNR6, A3N4F4, A3NQ45, A3PI90, A4JIT0, A4WUQ2, A5I6Z3, A5UXF9, A7FYL3, A7GIK2, A7NKM0, A8M5E6, A9AC51, A9KBI0, A9N8Z4, A9WCD8, B1INF7, B1K0H7, B1L1G9, B1YPV8, B2A5W7, B2JJW2, B2T1M4, B2U7V7, B3DWT4, B4E7X6, B6IZ25, B6J4H5, B8G974, B8HY89, B8J405, B9KPF8, B9LER8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PF-3845	down-regulates	FAAH	“chemical inhibition”
URB597	down-regulates	FAAH	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

102 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	59
Likely benign	11
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3065619	NM_001441.3(FAAH):c.549del (p.His184fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:46405122:A:C	S140R	0.997
1:46405124:C:A	S140R	0.997
1:46405124:C:G	S140R	0.997
1:46405730:A:C	S241R	0.997
1:46405732:C:A	S241R	0.997
1:46405732:C:G	S241R	0.997
1:46405719:A:T	D237V	0.996
1:46405718:G:C	D237H	0.995
1:46405767:G:A	G253D	0.993
1:46406259:G:A	G281D	0.993
1:46413083:A:C	S492R	0.993
1:46413085:C:A	S492R	0.993
1:46413085:C:G	S492R	0.993
1:46405718:G:T	D237Y	0.992
1:46405719:A:C	D237A	0.992
1:46405731:G:T	S241I	0.992
1:46413486:T:C	C551R	0.992
1:46405728:G:A	G240D	0.991
1:46405736:C:A	R243S	0.991
1:46405774:G:C	K255N	0.991
1:46405774:G:T	K255N	0.991
1:46413103:C:A	N498K	0.991
1:46413103:C:G	N498K	0.991
1:46413122:G:T	G505W	0.990
1:46413123:G:A	G505E	0.990
1:46413518:T:G	C561W	0.990
1:46405737:G:C	R243P	0.989
1:46405766:G:C	G253R	0.989
1:46405504:A:C	S193R	0.988
1:46405588:C:A	S193R	0.988

dbSNP variants (sampled 300 via entrez): RS1000118692 (1:46400304 G>A), RS1000247574 (1:46407204 G>A), RS1000401890 (1:46412971 T>C), RS1000510069 (1:46406060 G>A), RS1000579166 (1:46411997 C>A,T), RS1000636414 (1:46407195 G>T), RS1000706771 (1:46393810 A>G), RS1000777260 (1:46399836 T>G), RS1000808363 (1:46400072 G>C), RS1001138935 (1:46411808 C>G), RS1001389243 (1:46401843 C>T), RS1001495178 (1:46394758 G>A), RS1001568480 (1:46413302 G>A), RS1001736446 (1:46394962 C>A,T), RS1001751296 (1:46413682 G>A)

Disease associations

OMIM: gene MIM:602935 | disease phenotypes: MIM:606581

GenCC curated gene-disease

Mondo (1): polysubstance abuse, susceptibility to (MONDO:0011685)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST005951_37	Body mass index	8.000000e-10
GCST009165_1	Lipid or lipoprotein levels	2.000000e-08
GCST012020_28	Serum metabolite levels	5.000000e-56
GCST012020_29	Serum metabolite levels	1.000000e-13
GCST012020_553	Serum metabolite levels	2.000000e-31
GCST012020_554	Serum metabolite levels	6.000000e-12
GCST012020_67	Serum metabolite levels	2.000000e-97
GCST012020_71	Serum metabolite levels	3.000000e-83
GCST012021_26	Serum metabolite levels	2.000000e-31
GCST012021_27	Serum metabolite levels	6.000000e-12
GCST012298_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	3.000000e-06
GCST012301_3	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	3.000000e-06
GCST012353_8	Serum metabolite concentrations in chronic kidney disease	4.000000e-14
GCST012353_9	Serum metabolite concentrations in chronic kidney disease	6.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004574	total cholesterol measurement
EFO:0005105	lipid or lipoprotein measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2243 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 959,545 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL465	DRONABINOL	4	62,107
CHEMBL502	DONEPEZIL	4	43,493
CHEMBL526	PROPOFOL	4	28,835
CHEMBL636	RIVASTIGMINE	4	30,156
CHEMBL1079935	AMPEROZIDE	2	948
CHEMBL120563	THIRAM	2	79,340
CHEMBL1651534	REDAFAMDASTAT	2	102
CHEMBL4297294	JNJ-42165279	2	65
CHEMBL8659	OLEIC ACID	2	713,838
CHEMBL184238	URB-597	1	417
CHEMBL2386558	MK-3168	1	45
CHEMBL4297354	AZD-7687	1	199

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

8 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2295632	Toxicity	3	opioids
rs2295632	Toxicity	3	morphine
rs324420	Toxicity	3	aripiprazole;clozapine;haloperidol;olanzapine;quetiapine;risperidone	Psychotic Disorder
rs324420	Toxicity	3	cannabinoids	Substance-Related Disorders
rs324420	Other	3	methamphetamine	Substance-Related Disorders
rs324420	Toxicity	3	morphine	Constipation;Delirium;Lung Neoplasms;Nausea;Pain;Postoperative Nausea and Vomiting;Pruritus;Respiratory Insufficiency;Somnolence;Urinary Retention
rs3766246	Toxicity	3	morphine
rs4141964	Toxicity	3	morphine

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs324420	FAAH	3	5.25	4	aripiprazole;clozapine;haloperidol;olanzapine;quetiapine;risperidone;methamphetamine;morphine;cannabinoids
rs2295632	FAAH	3	3.00	2	opioids;morphine
rs11576941	FAAH		0.00	0
rs45586133	FAAH		0.00	0
rs4141964	FAAH	3	3.00	1	morphine
rs3766246	FAAH	3	3.00	1	morphine
rs2295633	FAAH		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (23 total), top 23:

Ligand	Action	Affinity	Parameter
UCM1341	Inhibition	9.07	pIC50
PF-04457845	Inhibition	9.0	pIC50
JNJ40355003	Inhibition	8.85	pIC50
SA-57	Inhibition	8.72	pIC50
URB937	Inhibition	8.7	pIC50
JZL195	Inhibition	8.7	pIC50
ASP8477	Inhibition	8.4	pIC50
compound 19y [Kiss et al., 2011]	Inhibition	8.22	pIC50
PF750	Inhibition	8.19	pIC50
(S)-ARN2508	Inhibition	8.03	pIC50
(R)-ARN2508	Inhibition	8.0	pIC50
CAY10499	Inhibition	7.85	pIC50
JNJ1661010	Inhibition	7.8	pIC50
dual sEH/FAAH inhibitor 11	Inhibition	7.43	pKi
example 13 [WO2009109743]	Inhibition	7.42	pIC50
OL135	Inhibition	7.4	pIC50
BIA 10-2474	Inhibition	7.3	pIC50
BIA 10-2639	Inhibition	7.3	pIC50
JNJ-42165279	Inhibition	7.12	pIC50
URB597	Inhibition	7.0	pIC50
MM-433593	Inhibition	7.0	pIC50
FP-Rh	Binding	6.63	pEC50
PF3845	Inhibition	6.6	pIC50

Binding affinities (BindingDB)

621 measured of 800 human assays (896 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyrimidine-5-carboxamide	IC50	0.8 nM	US-9682953: Amide compounds, compositions and applications thereof
2-amino-N-[4-[[3-[(5-chloro-6-methyl-2-pyridinyl)oxy]phenyl]methylidene]cyclohexyl]pyrimidine-5-carboxamide	IC50	1.1 nM	US-9682953: Amide compounds, compositions and applications thereof
N-pyridazin-3-yl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]piperidine-1-carboxamide	IC50	1.9 nM	US-12378231: Small molecules as monoacylglycerol lipase (MAGL) inhibitors, compositions and use thereof
2-fluorophenyl N-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamate	IC50	2 nM
6-amino-N-[4-[[3-[[6-chloro-5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyridine-3-carboxamide	IC50	3 nM	US-9682953: Amide compounds, compositions and applications thereof
3-[[5-[3-(2-phenylmethoxyethoxy)phenyl]-2-pyridinyl]oxy]-N-pyridazin-3-ylazetidine-1-carboxamide	IC50	3 nM	US-9006269: Azetidine derivatives
6-(methylamino)-N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyridine-3-carboxamide	IC50	4 nM	US-9682953: Amide compounds, compositions and applications thereof
5-(4-chlorophenyl)sulfanyl-4-(1H-indazol-5-yl)-2-(oxan-4-yl)-1,3-oxazole	IC50	4.19 nM	US-9193697: Oxazole derivatives useful as modulators of FAAH
2-fluorophenyl N-[7-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)heptan-2-yl]carbamate	IC50	4.2 nM
phenyl N-[6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamate	IC50	5.3 nM
ethyl 5-(3-((tetradecylcarbamoyl)oxy)phenyl)nicotinate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
methyl 5-(3-((heptylcarbamoyl)oxy)phenyl)nicotinate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
methyl 5-(3-((octylcarbamoyl)oxy)phenyl)nicotinate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(furan-2-yl)pyridin-3-yl)phenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(oxazol-2-yl)pyridin-3-yl)phenyl heptylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(oxazol-2-yl)pyridin-3-yl)phenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(isoxazol-5-yl)pyridin-3-yl)phenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(isoxazol-5-yl) pyridin-3-yl)-4-methoxyphenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)134 pyridine-3-yl)phenyl heptylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridine-3-yl)phenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)-4-hydroxyphenyl heptylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)-4-hydroxyphenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)-5-hydroxyphenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)-4-methoxyphenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)-5-methoxyphenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)-5-fluorophenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-thiadiazol-2-yl)pyridin-3-yl)phenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1,3,4-thiadiazol-2-yl)pyridin-3-yl)-4-methoxyphenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1H-1,2,4-triazol-5-yl)pyridin-3-yl)phenyl octyl carbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(5-(1H-1,2,4-triazol-5-yl)pyridin-3-yl)-4-hydroxyphenyl octyl carbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(4-(1,3,4-oxadiazol-2-yl)pyridin-2-yl)phenyl heptylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
3-(6-(1,3,4-oxadiazol-2-yl)pyrazin-2-yl)phenyl octylcarbamate	IC50	5.5 nM	US-20250129027: FATTY ACID AMIDE HYDROLASE MODULATORS, COMPOSITIONS COMPRISING THE SAME AND USES THEREOF
5-chloro-N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyridine-3-carboxamide	IC50	6 nM	US-9682953: Amide compounds, compositions and applications thereof
3-[[5-[2-chloro-5-(2-methoxyethoxy)phenyl]-2-pyridinyl]oxy]-N-pyridazin-3-ylazetidine-1-carboxamide	IC50	7 nM	US-9006269: Azetidine derivatives
CHEMBL2414027	IC50	8 nM
4-[5-(4-chlorophenyl)sulfanyl-4-(4-methylsulfinylphenyl)-1,3-oxazol-2-yl]cyclohex-3-en-1-ol	IC50	8.68 nM	US-9193697: Oxazole derivatives useful as modulators of FAAH
N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyrazine-2-carboxamide	IC50	9 nM	US-9682953: Amide compounds, compositions and applications thereof
6-(dimethylamino)-N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyridine-3-carboxamide	IC50	9 nM	US-9682953: Amide compounds, compositions and applications thereof
3-[[5-[3-(2-methoxyethoxy)phenyl]-2-pyridinyl]oxy]-N-pyrimidin-4-ylazetidine-1-carboxamide	IC50	9 nM	US-9006269: Azetidine derivatives
4-[[3-(4-methoxyphenoxy)phenyl]methyl]-N-phenylpiperazine-1-carboxamide	IC50	9 nM	US-9169224: Piperazinyl and piperidinyl ureas as modulators of fatty acid amide hydrolase
4-[[3-(4-chlorophenoxy)phenyl]methyl]-N-phenylpiperazine-1-carboxamide	IC50	9 nM	US-9169224: Piperazinyl and piperidinyl ureas as modulators of fatty acid amide hydrolase
5-(4-chlorophenyl)sulfanyl-2-(oxan-4-yl)-4-(6-piperazin-1-yl-3-pyridinyl)-1,3-oxazole	IC50	9.61 nM	US-9193697: Oxazole derivatives useful as modulators of FAAH
N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyridazine-4-carboxamide	IC50	10 nM	US-9682953: Amide compounds, compositions and applications thereof
2-fluorophenyl N-{6-[4,5-bis(4-fluorophenyl)-2-methyl-1H-imidazol-1-yl]hexyl}carbamate	IC50	10 nM
ethyl 7-(2-ethyl-4,5-diphenyl-1H-imidazol-1-yl)heptanoate	IC50	11 nM
5-(4-chlorophenyl)sulfanyl-2-(cyclohexen-1-yl)-4-(4-methylsulfinylphenyl)-1,3-oxazole	IC50	11.9 nM	US-9193697: Oxazole derivatives useful as modulators of FAAH
6-(2H-tetrazol-5-yl)-N-[4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methylidene]cyclohexyl]pyridine-3-carboxamide	IC50	12 nM	US-9682953: Amide compounds, compositions and applications thereof
3-[[5-(2,5-dimethoxyphenyl)-2-pyridinyl]oxy]-N-pyridazin-3-ylazetidine-1-carboxamide	IC50	12 nM	US-9006269: Azetidine derivatives
3-[[5-(2-methoxyphenyl)-2-pyridinyl]oxy]-N-pyridazin-3-ylazetidine-1-carboxamide	IC50	12 nM	US-9006269: Azetidine derivatives

ChEMBL bioactivities

2652 potent at pChembl≥5 of 2881 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3798535
11.00	IC50	0.01	nM	CHEMBL3797772
10.89	Ki	0.013	nM	CHEMBL3798476
10.89	Ki	0.0128	nM	CHEMBL3798476
10.83	Ki	0.0147	nM	CHEMBL3798355
10.73	Ki	0.0185	nM	CHEMBL3800599
10.73	Ki	0.0185	nM	CHEMBL3799008
10.73	Ki	0.0185	nM	CHEMBL3799516
10.70	IC50	0.02	nM	CHEMBL3798487
10.60	IC50	0.025	nM	CHEMBL3113272
10.52	IC50	0.03	nM	CHEMBL3797635
10.47	Ki	0.0336	nM	CHEMBL3797226
10.42	Ki	0.0383	nM	CHEMBL3797377
10.40	IC50	0.04	nM	CHEMBL3800456
10.25	Ki	0.056	nM	CHEMBL3798594
10.25	Ki	0.0563	nM	CHEMBL3798594
10.22	IC50	0.06	nM	CHEMBL3797841
10.15	IC50	0.07	nM	CHEMBL3798156
10.14	IC50	0.072	nM	CHEMBL3113271
10.10	IC50	0.08	nM	CHEMBL3113274
10.10	IC50	0.08	nM	CHEMBL3799744
10.05	IC50	0.09	nM	CHEMBL3797809
10.03	Ki	0.094	nM	CHEMBL175854
10.03	IC50	0.093	nM	CHEMBL1812722
10.00	IC50	0.1	nM	CHEMBL182199
10.00	IC50	0.1	nM	CHEMBL112486
9.85	IC50	0.14	nM	CHEMBL3798476
9.83	Ki	0.147	nM	CHEMBL3799633
9.82	IC50	0.15	nM	CHEMBL598764
9.80	IC50	0.16	nM	CHEMBL3798355
9.80	IC50	0.16	nM	CHEMBL4078217
9.70	IC50	0.2	nM	CHEMBL3800599
9.70	IC50	0.2	nM	CHEMBL3799008
9.70	IC50	0.2	nM	CHEMBL3799516
9.70	Ki	0.2	nM	CHEMBL175854
9.70	Ki	0.2	nM	CHEMBL272111
9.70	IC50	0.2	nM	CHEMBL597648
9.62	IC50	0.24	nM	URB-597
9.60	IC50	0.25	nM	CHEMBL597430
9.60	IC50	0.25	nM	CHEMBL596658
9.59	Ki	0.26	nM	CHEMBL272111
9.57	IC50	0.27	nM	CHEMBL597647
9.55	Ki	0.28	nM	CHEMBL367966
9.54	Ki	0.29	nM	CHEMBL178398
9.52	IC50	0.3	nM	CHEMBL2386566
9.52	IC50	0.3	nM	CHEMBL367966
9.52	IC50	0.3	nM	CHEMBL179760
9.52	Ki	0.3	nM	CHEMBL464186
9.48	IC50	0.33	nM	METHOXYARACHIDONOYL FLUOROPHOSPHONATE
9.48	IC50	0.3311	nM	METHOXYARACHIDONOYL FLUOROPHOSPHONATE

PubChem BioAssay actives

1873 with measured affinity, of 3284 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2-methylphenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	<0.0001	uM
(3-chlorophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(4-methylphenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(4-cyanophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(3-cyanophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	<0.0001	uM
(4-chlorophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
[4-(trifluoromethyl)phenyl] 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(3-cyanophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperazine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(4-chlorophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperazine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	<0.0001	uM
[4-(trifluoromethyl)phenyl] 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperazine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(4-nitrophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperazine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(4-methoxyphenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	<0.0001	uM
(4-cyanophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperazine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
pyridin-3-yl 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	<0.0001	uM
phenyl 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
(2-chlorophenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	<0.0001	uM
4-[4-(2,5-difluorophenyl)pyrimidin-2-yl]-N-pyridazin-3-ylpiperazine-1-carboxamide	1069557: Apparent inhibition of human FAAH expressed in CHOK1 cells using AMCAA as substrate after 30 mins by fluorescence assay	ic50	<0.0001	uM
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraene-1-sulfonyl fluoride	241871: Irreversible inhibition of fatty acid amide hydrolase	ic50	0.0001	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-6-phenylhexan-1-one	238532: Binding affinity for human fatty acid amide hydrolase	ki	0.0001	uM
(3-methylphenyl) 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	0.0001	uM
phenyl 4-[4-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperazine-1-carboxylate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ki	0.0001	uM
[(E)-pyridin-3-ylmethylideneamino] N-(4-undecoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0001	uM
[4-[4-[(3-fluorophenyl)methoxy]phenoxy]piperidin-1-yl]-imidazol-1-ylmethanone	612783: Inhibition of FAAH	ic50	0.0001	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-9-phenylnonan-1-one	241829: Inhibitory concentration of fatty acid amide hydrolase using FP-Rh radioligand	ic50	0.0001	uM
4-[4-(3,5-difluorophenyl)pyrimidin-2-yl]-N-pyridazin-3-ylpiperazine-1-carboxamide	1069557: Apparent inhibition of human FAAH expressed in CHOK1 cells using AMCAA as substrate after 30 mins by fluorescence assay	ic50	0.0001	uM
4-[4-(2,3-difluorophenyl)pyrimidin-2-yl]-N-pyridazin-3-ylpiperazine-1-carboxamide	1069557: Apparent inhibition of human FAAH expressed in CHOK1 cells using AMCAA as substrate after 30 mins by fluorescence assay	ic50	0.0001	uM
1,1,1,3,3,3-hexafluoropropan-2-yl 3-(1-benzylpyrazol-3-yl)azetidine-1-carboxylate	1477448: Inhibition of human recombinant FAAH using arachidonoyl-AMC as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0002	uM
[3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	0.0002	uM
[(E)-(4-fluorophenyl)methylideneamino] N-(4-nonoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0002	uM
2-[3-(4-phenylphenyl)propanoyl]-1,3-oxazole-5-carbonitrile	346660: Inhibition of FAAH	ki	0.0002	uM
(5Z,8Z,11Z,14Z)-1-[fluoro(methoxy)phosphoryl]icosa-5,8,11,14-tetraene	439742: Inhibition of human FAAH	ic50	0.0003	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-7-phenylheptan-1-one	241449: Inhibitory concentration against Fatty-acid amide hydrolase	ic50	0.0003	uM
7-phenyl-1-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)heptan-1-one	409628: Inhibition of FAAH at pH 9	ki	0.0003	uM
[(E)-pyridin-3-ylmethylideneamino] N-(4-decoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0003	uM
[(E)-pyridin-3-ylmethylideneamino] N-(4-dodecoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0003	uM
[(E)-(4-fluorophenyl)methylideneamino] N-(4-decoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0003	uM
[(E)-(4-fluorophenyl)methylideneamino] N-(4-octoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0003	uM
[(E)-benzylideneamino] N-(4-decoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0003	uM
[(E)-benzylideneamino] N-(4-nonoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0003	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-8-phenyloctan-1-one	241829: Inhibitory concentration of fatty acid amide hydrolase using FP-Rh radioligand	ic50	0.0003	uM
1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-5-phenylpentan-1-one	346660: Inhibition of FAAH	ki	0.0003	uM
trans-(1S,2S)-2-[4-[5-(4-chlorophenyl)sulfanyl-1-methylimidazol-4-yl]phenyl]-N,N-dimethylcyclopropane-1-carboxamide	748651: Inhibition of human FAAH expressed in CHO cell lysates assessed as arachidonyl-7-amino-4-methylcoumarin amide hydrolysis to 7-amino 4-methyl coumarin preincubated for 15 mins prior to substrate addition measured after 1 to 3 hrs by fluorescence assay	ic50	0.0003	uM
7-phenyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one	1298614: Inhibition of MBP-fused human recombinant FAAH with truncated N-terminal transmembrane domain expressed in Escherichia coli T7 using D-AMC substrate measured over 40 mins by fluorescence based assay	ic50	0.0004	uM
3-[[4-(3-methoxyphenyl)phenyl]methoxy]-3-methylazetidine-1-carbonitrile	1650208: Inhibition of recombinant human FAAH expressed in Escherichia coli using fluorogenic AAMCA as substrate by fluorimetric assay	ic50	0.0004	uM
2-(7-phenylheptanoyl)-1,3-oxazole-5-carbonitrile	280028: Inhibition of rat recombinant FAAH expressed in Escherichia coli by [14C]oleamide breakdown	ki	0.0004	uM
1-(1,3-oxazol-2-yl)-4-[1-[(3-phenoxyphenyl)methyl]piperidin-4-yl]butan-1-one	346666: Inhibition of human FAAH	ic50	0.0004	uM
3-(4-phenylmethoxyphenyl)-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)propan-1-one	1798285: FAAH Inhibition Assay from Article 10.1021/jm061414r: “Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.”	ki	0.0004	uM
[(E)-(4-fluorophenyl)methylideneamino] N-(4-undecoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0004	uM
[(E)-benzylideneamino] N-(4-octoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0004	uM
[(E)-benzylideneamino] N-(4-undecoxyphenyl)carbamate	459762: Inhibition of human FAAH expressed in human H4 cells	ic50	0.0004	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Dronabinol	affects expression, affects response to substance	3
bisphenol A	decreases activity	2
ASP8477	decreases activity	1
triphenyl phosphate	affects expression	1
propylparaben	decreases activity	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	decreases activity	1
sodium arsenite	increases expression	1
1,6-bis(cyclohexyloximinocarbonyl)hexane	decreases activity	1
butylparaben	decreases activity	1
benzylparaben	decreases activity	1
4-phenylbutyric acid	increases expression	1
heptylparaben	decreases activity	1
cyclohexyl carbamic acid 3’-carbamoylbiphenyl-3-yl ester	decreases activity	1
cannabidivarin	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Amphetamine	affects response to substance	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cannabidiol	decreases expression	1
Progesterone	increases activity, increases expression	1
Selenium	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Endocannabinoids	increases metabolic processing	1

ChEMBL screening assays

363 unique, capped per target: 352 binding, 11 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1022294	Binding	Inhibition of human recombinant FAAH expressed in HEK293 cells by [3H]anandamide carbon filtration assay	Synthesis and evaluation of benzothiazole-based analogues as novel, potent, and selective fatty acid amide hydrolase inhibitors. — J Med Chem
CHEMBL3790989	ADMET	Drug metabolism assessed as human recombinant N-terminal FLAG/C-terminal His-tagged FAAH1 (32 to 579 residues)-mediated compound hydrolysis by measuring release of EPA at 25 uM by LC/MS-MS analysis	Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.