View source for Fatty acid amide hydrolase

{{redirect|FAAH}}
{{Infobox_gene}}
'''Fatty acid amide hydrolase''' or '''FAAH''' ({{EC number|3.5.1.99}}, oleamide hydrolase, anandamide amidohydrolase) is a member of the [[serine hydrolase]] family of [[enzyme]]s. It was first shown to break down [[anandamide]] in 1993.<ref name="pmid8373432">{{cite journal | vauthors = Deutsch DG, Chin SA | title = Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist | journal = Biochemical Pharmacology | volume = 46 | issue = 5 | pages = 791–6 | date = September 1993 | pmid = 8373432 | doi = 10.1016/0006-2952(93)90486-G }}</ref> In humans, it is encoded by the [[gene]] ''FAAH''.<ref name="pmid8900284">{{cite journal | vauthors = Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB | title = Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides | journal = Nature | volume = 384 | issue = 6604 | pages = 83–7 | date = November 1996 | pmid = 8900284 | doi = 10.1038/384083a0 }}</ref><ref name="pmid9122178">{{cite journal | vauthors = Giang DK, Cravatt BF | title = Molecular characterization of human and mouse fatty acid amide hydrolases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 6 | pages = 2238–42 | date = March 1997 | pmid = 9122178 | pmc = 20071 | doi = 10.1073/pnas.94.6.2238 }}</ref><ref name="pmid12459591">{{PDB|1MT5}}; {{cite journal | vauthors = Bracey MH, Hanson MA, Masuda KR, Stevens RC, Cravatt BF | title = Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling | journal = Science | volume = 298 | issue = 5599 | pages = 1793–6 | date = November 2002 | pmid = 12459591 | doi = 10.1126/science.1076535 }}</ref>

== Function ==

FAAH is an integral membrane hydrolase with a single ''N''-terminal transmembrane domain. ''In vitro'', FAAH has esterase and amidase activity.<ref name="pmid10571985">{{cite journal | vauthors = Patricelli MP, Cravatt BF | title = Fatty acid amide hydrolase competitively degrades bioactive amides and esters through a nonconventional catalytic mechanism | journal = Biochemistry | volume = 38 | issue = 43 | pages = 14125–30 | date = October 1999 | pmid = 10571985 | doi = 10.1021/bi991876p }}</ref> ''In vivo'', FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of the FAAs include:

* [[Anandamide]] (''N''-arachidonoylethanolamine), an [[endocannabinoid]]<ref name="pmid11470906">{{cite journal | vauthors = Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, Lichtman AH | title = Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 16 | pages = 9371–6 | date = July 2001 | pmid = 11470906 | pmc = 55427 | doi = 10.1073/pnas.161191698 }}</ref>
*[[2-Arachidonoylglycerol|2-arachidonoylglycerol]] (2-AG), an endocannabinoid.<ref>{{Cite journal|date=2000-11-01|title=The fatty acid amide hydrolase (FAAH)|url=https://www.sciencedirect.com/science/article/pii/S0009308400001900|journal=Chemistry and Physics of Lipids|language=en|volume=108|issue=1-2|pages=107–121|doi=10.1016/S0009-3084(00)00190-0|issn=0009-3084}}</ref>
* Other [[N-acylethanolamine|''N''-acylethanolamines]], such as [[Oleoylethanolamide|''N''-oleoylethanolamine]] and [[Palmitoylethanolamide|''N''-palmitoylethanolamine]]<ref name="pmid15533037">{{cite journal | vauthors = Saghatelian A, Trauger SA, Want EJ, Hawkins EG, Siuzdak G, Cravatt BF | title = Assignment of endogenous substrates to enzymes by global metabolite profiling | journal = Biochemistry | volume = 43 | issue = 45 | pages = 14332–9 | date = November 2004 | pmid = 15533037 | doi = 10.1021/bi0480335 }}</ref>
* The sleep-inducing lipid [[oleamide]]<ref name="pmid7770779">{{cite journal | vauthors = Cravatt BF, Prospero-Garcia O, Siuzdak G, Gilula NB, Henriksen SJ, Boger DL, Lerner RA | title = Chemical characterization of a family of brain lipids that induce sleep | journal = Science | volume = 268 | issue = 5216 | pages = 1506–9 | date = June 1995 | pmid = 7770779 | doi = 10.1126/science.7770779 }}</ref>
* The ''N''-acyltaurines, which are agonists of the [[transient receptor potential]] (TRP) family of calcium channels.<ref name="pmid16866345">{{cite journal | vauthors = Saghatelian A, McKinney MK, Bandell M, Patapoutian A, Cravatt BF | title = A FAAH-regulated class of N-acyl taurines that activates TRP ion channels | journal = Biochemistry | volume = 45 | issue = 30 | pages = 9007–15 | date = August 2006 | pmid = 16866345 | doi = 10.1021/bi0608008 }}</ref>

''FAAH'' [[Knockout mouse|knockout mice]] display highly elevated (>15-fold) levels of ''N''-acylethanolamines and ''N''-acyltaurines in various tissues. Because of their significantly elevated anandamide levels, ''FAAH'' KOs have an analgesic phenotype, showing reduced pain sensation in the [[hot plate test]], the [[formalin]] test, and the [[tail flick test]].<ref name="pmid15362158">{{cite journal | vauthors = Cravatt BF, Lichtman AH | title = The endogenous cannabinoid system and its role in nociceptive behavior | journal = Journal of Neurobiology | volume = 61 | issue = 1 | pages = 149–60 | date = October 2004 | pmid = 15362158 | doi = 10.1002/neu.20080 }}</ref> Finally, because of their impaired ability to degrade anandamide, ''FAAH'' KOs also display supersensitivity to [[exogenous]] anandamide, a cannabinoid receptor (CB) agonist.<ref name="pmid11470906"/>

Due to the ability of FAAH to regulate [[nociception]], it is currently viewed as an attractive drug target for the treatment of pain.<ref name="pmid24275607">{{cite journal | vauthors = Sałaga M, Sobczak M, Fichna J | title = Inhibition of fatty acid amide hydrolase (FAAH) as a novel therapeutic strategy in the treatment of pain and inflammatory diseases in the gastrointestinal tract | journal = European Journal of Pharmaceutical Sciences | volume = 52 | issue = | pages = 173–9 | year = 2014 | pmid = 24275607 | doi = 10.1016/j.ejps.2013.11.012 }}</ref><ref name="pmid25207181">{{cite journal | vauthors = Ulugöl A | title = The endocannabinoid system as a potential therapeutic target for pain modulation | journal = Balkan Medical Journal | volume = 31 | issue = 2 | pages = 115–20 | year = 2014 | pmid = 25207181 | pmc = 4115931 | doi = 10.5152/balkanmedj.2014.13103 }}</ref><ref name="pmid25998048">{{cite journal | vauthors = Ghosh S, Kinsey SG, Liu QS, Hruba L, McMahon LR, Grim TW, Merritt CR, Wise LE, Abdullah RA, Selley DE, Sim-Selley LJ, Cravatt BF, Lichtman AH | display-authors = 6 | title = Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 354 | issue = 2 | pages = 111–20 | year = 2015 | pmid = 25998048 | pmc = 4518073 | doi = 10.1124/jpet.115.222851 }}</ref>

A mutation in FAAH was initially provisionally linked to drug abuse and dependence but this was not borne out in subsequent studies.<ref name=Panlilio2013rev>{{cite journal | vauthors = Panlilio LV, Justinova Z, Goldberg SR | title = Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction | journal = Pharmacology & Therapeutics | volume = 138 | issue = 1 | pages = 84–102 | year = 2013 | pmid = 23333350 | pmc = 3662489 | doi = 10.1016/j.pharmthera.2013.01.003 }}</ref>

Studies in cells and animals and genetic studies in humans have shown that inhibiting FAAH may be a useful strategy to treat [[anxiety disorders]].<ref name=Panlilio2013rev/><ref name="pmid24325918">{{cite journal | vauthors = Gunduz-Cinar O, Hill MN, McEwen BS, Holmes A | title = Amygdala FAAH and anandamide: mediating protection and recovery from stress | journal = Trends in Pharmacological Sciences | volume = 34 | issue = 11 | pages = 637–44 | date = November 2013 | pmid = 24325918 | pmc = 4169112 | doi = 10.1016/j.tips.2013.08.008 }}</ref><ref name="pmid27456243">{{cite journal | vauthors = Berardi A, Schelling G, Campolongo P | title = The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): From preclinical findings to innovative therapeutic approaches in clinical settings | journal = Pharmacological Research | volume = 111 | issue =  | pages = 668–78 | date = September 2016 | pmid = 27456243 | doi = 10.1016/j.phrs.2016.07.024 }}</ref>

== Inhibitors and inactivators ==
<!--
PLEASE DO NOT ADD UNSOURCED INFORMATION TO THIS SECTION, AND PLEASE MOVE THE SECTION TOWARD **SECONDARY SOURCES**. IN ALL CASES, BE CAREFUL TO REFLECT SPECIFICALLY WHAT IS SAID IN THE PUBLICATION. PRIMARY SOURCES SHOULD BE ACCOMPANIED BY STATMENTS LIKE, "In one report…" RATHER THAN STATING A FIRM CONCLUSION BASED ON ONE PRIMARY SOURCE. MOREOVER, TERMS LIKE "SELECTIVE", STATED PERFUNCTORILY, ARE NEAR MEANINGLESS; SOME DATA NEEDS BE STATED, AND/OR A COMPARISON TO OTHER MORE ESTABLISHED AGENTS.
-->

Based on the hydrolytic mechanism of fatty acid amide hydrolase, a large number of [[Enzyme inhibitor#Irreversible inhibitors|irreversible]] and [[Enzyme inhibitor#Reversible inhibitors|reversible]] inhibitors of this enzyme have been developed.<ref name="pmid19367506">{{cite journal | vauthors = Janero DR, Vadivel SK, Makriyannis A | title = Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: drug-discovery strategies | journal = International Review of Psychiatry (Abingdon, England) | volume = 21 | issue = 2 | pages = 122–33 | date = April 2009 | pmid = 19367506 | pmc = 5531754 | doi = 10.1080/09540260902782778 }}</ref><ref name="pmid20544003">{{cite journal | vauthors = Ahn K, Johnson DS, Cravatt BF | title = Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders | journal = Expert Opinion on Drug Discovery | volume = 4 | issue = 7 | pages = 763–784 | date = July 2009 | pmid = 20544003 | pmc = 2882713 | doi = 10.1517/17460440903018857 }}</ref><ref name="pmid20047159">{{cite journal | vauthors = Petrosino S, Di Marzo V | title = FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels | journal = Current Opinion in Investigational Drugs | volume = 11 | issue = 1 | pages = 51–62 | date = January 2010 | pmid = 20047159 | doi =  }}</ref><ref name="pmid20370710">{{cite journal | vauthors = Minkkilä A, Saario S, Nevalainen T | title = Discovery and development of endocannabinoid-hydrolyzing enzyme inhibitors | journal = Current Topics in Medicinal Chemistry | volume = 10 | issue = 8 | pages = 828–58 | year = 2010 | pmid = 20370710 | doi =  10.2174/156802610791164238}}</ref><ref name="pmid21631410">{{cite journal | vauthors = Khanna IK, Alexander CW | title = Fatty acid amide hydrolase inhibitors--progress and potential | journal = CNS & Neurological Disorders Drug Targets | volume = 10 | issue = 5 | pages = 545–58 | date = August 2011 | pmid = 21631410 | doi = 10.2174/187152711796234989 }}</ref><ref name="pmid23488865">{{cite journal | vauthors = Bisogno T, Maccarrone M | title = Latest advances in the discovery of fatty acid amide hydrolase inhibitors | journal = Expert Opinion on Drug Discovery | volume = 8 | issue = 5 | pages = 509–22 | date = May 2013 | pmid = 23488865 | doi = 10.1517/17460441.2013.780021 }}</ref><ref name="pmid24135210">{{cite journal | vauthors = Pertwee RG | title = Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications | journal = The Proceedings of the Nutrition Society | volume = 73 | issue = 1 | pages = 96–105 | date = February 2014 | pmid = 24135210 | doi = 10.1017/S0029665113003649 }}</ref><ref name="pmid26413912">{{cite journal | vauthors = Lodola A, Castelli R, Mor M, Rivara S | title = Fatty acid amide hydrolase inhibitors: a patent review (2009-2014) | journal = Expert Opinion on Therapeutic Patents | volume = 25 | issue = 11 | pages = 1247–66 | year = 2015 | pmid = 26413912 | doi = 10.1517/13543776.2015.1067683 }}</ref>

Some of the more significant compounds are listed below;

{{div col|colwidth=33em}}
* [[AM374]], palmitylsulfonyl fluoride, one of the first FAAH inhibitors developed for ''in vitro'' use, but too reactive for research ''in vivo'' 
* [[ARN2508]], derivative of [[flurbiprofen]], dual FAAH / COX inhibitor
* [[BIA 10-2474]] ([[Bial |Bial-Portela]] & Ca. SA, [[Portugal]]) has been linked to severe adverse events affecting 5 patients in a drug trial in Rennes, France, and at least one death, in January 2016.<ref>{{Cite journal  | pmid = | pmc = | year = 2016 | author1 = Enserink | first1 = Martin | name-list-format = vanc | title = More Details Emerge on Fateful French Drug Trial | journal = [[Science (magazine)|Science]] | format = online | volume = | issue = January 16 | pages = | url = http://www.sciencemag.org/news/2016/01/more-details-emerge-fateful-french-drug-trial | access-date = 16 January 2016 | doi = 10.1126/science.aae0247 }}</ref>  Many other pharmaceutical companies have previously taken other FAAH inhibitors into clinical trials without reporting such adverse events.
* [[BMS-469908]]<ref name="pmid23512546">{{cite journal | vauthors = Blankman JL, Cravatt BF | title = Chemical probes of endocannabinoid metabolism | journal = Pharmacological Reviews | volume = 65 | issue = 2 | pages = 849–71 | date = April 2013 | pmid = 23512546 | pmc = 3639726 | doi = 10.1124/pr.112.006387 }}</ref>
* [[CAY-10402]]
* [[JNJ-245]]
* [[JNJ-1661010]]<ref name="pmid21502526">{{cite journal | vauthors = Min X, Thibault ST, Porter AC, Gustin DJ, Carlson TJ, Xu H, Lindstrom M, Xu G, Uyeda C, Ma Z, Li Y, Kayser F, Walker NP, Wang Z | title = Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 18 | pages = 7379–84 | date = May 2011 | pmid = 21502526 | pmc = 3088576 | doi = 10.1073/pnas.1016167108 }}</ref>
* [[JNJ-28833155]]
* [[JNJ-40413269]]
* [[JNJ-42119779]]
* [[JNJ-42165279]] in clinical trials against social anxiety and depression,<ref name="pmid26713105">{{cite journal | vauthors = Keith JM, Jones WM, Tichenor M, Liu J, Seierstad M, Palmer JA, Webb M, Karbarz M, Scott BP, Wilson SJ, Luo L, Wennerholm ML, Chang L, Rizzolio M, Rynberg R, Chaplan SR, Breitenbucher JG | title = Preclinical Characterization of the FAAH Inhibitor JNJ-42165279 | journal = ACS Medicinal Chemistry Letters | volume = 6 | issue = 12 | pages = 1204–8 | date = December 2015 | pmid = 26713105 | pmc = 4677372 | doi = 10.1021/acsmedchemlett.5b00353 }}</ref> trials suspended as a precautionary measure following serious adverse event with BIA 10-2474<ref>{{cite web |url=http://www.janssen.com/janssen-research-development-llc-voluntarily-suspends-dosing-phase-2-clinical-trials-experimental|title=Janssen Research & Development, LLC Voluntarily Suspends Dosing in Phase 2 Clinical Trials of Experimental Treatment for Mood Disorders|publisher=Janssen.com |date=17 January 2016 |accessdate=21 January 2016}}</ref>
* [[LY-2183240]] <ref>{{cite journal | vauthors = Moore SA, Nomikos GG, Dickason-Chesterfield AK, Schober DA, Schaus JM, Ying BP, Xu YC, Phebus L, Simmons RM, Li D, Iyengar S, Felder CC | title = Identification of a high-affinity binding site involved in the transport of endocannabinoids | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 49 | pages = 17852–7 | date = December 2005 | pmid = 16314570 | pmc = 1295594 | doi = 10.1073/pnas.0507470102 }}</ref>
* [[Cannabidiol]]<ref name="CamposMoreira2012">{{cite journal | vauthors = Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS | title = Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 367 | issue = 1607 | pages = 3364–78 | date = December 2012 | pmid = 23108553 | pmc = 3481531 | doi = 10.1098/rstb.2011.0389 }}</ref>
* [[MK-3168]]
* [[MK-4409]]
* [[MM-433593]]
* [[OL-92]]
* [[OL-135]]
* [[PF-622]]
* [[PF-750]] <ref name="pmid17949010"/> 
* [[PF-3845]]
* [[PF-04457845]] "exquisitely selective" for FAAH over other serine hydrolases, but failed in clinical trials against [[osteoarthritis]]<ref name="pmid26408159">{{cite journal | vauthors = Fowler CJ | title = The Potential of Inhibitors of Endocannabinoid Metabolism for Drug Development: A Critical Review | journal = Handbook of Experimental Pharmacology | volume = 231 | issue =  | pages = 95–128 | year = 2015 | pmid = 26408159 | doi = 10.1007/978-3-319-20825-1_4 | series = Handbook of Experimental Pharmacology | isbn = 978-3-319-20824-4 }}</ref>
* [[PF-04862853]]
* [[RN-450]]
* [[SA-47]]
* [[SA-73]]
* [[SSR-411298]] well tolerated in clinical trials but insufficient efficacy against depression, subsequently trialled against cancer pain as an adjunctive treatment.<ref>{{ClinicalTrialsGov|NCT00822744|An Eight-week Study of SSR411298 as Treatment for Major Depressive Disorder in Elderly Patients (FIDELIO)}}</ref><ref>{{cite web | url = https://www.clinicaltrialsregister.eu/ctr-search/search?query=SSR411298 | title = Clinical trials for SSR411298. | work = EU Clinical Trials Register}}</ref>
* [[ST-4068]], reversible inhibitor of FAAH
* [[TK-25]]
* [[URB524]]
* [[URB597]] (KDS-4103, [[Kadmus Pharmaceuticals]]), is an irreversible inactivator with a carbamate-based mechanism, and appears in one report as a somewhat selective, though it also inactivates other serine hydrolases (e.g., carboxylesterases) in peripheral tissues.<ref name="pmid17949010">{{cite journal | vauthors = Ahn K, Johnson DS, Fitzgerald LR, Liimatta M, Arendse A, Stevenson T, Lund ET, Nugent RA, Nomanbhoy TK, Alexander JP, Cravatt BF | title = Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity | journal = Biochemistry | volume = 46 | issue = 45 | pages = 13019–30 | date = November 2007 | pmid = 17949010 | doi = 10.1021/bi701378g }}</ref> 
* [[URB694]]
* [[URB937]]
* [[VER-156084]] ([[Vernalis plc|Vernalis]])<ref name="pmid19515560">{{cite journal | vauthors = Hart T, Macias AT, Benwell K, Brooks T, D'Alessandro J, Dokurno P, Francis G, Gibbons B, Haymes T, Kennett G, Lightowler S, Mansell H, Matassova N, Misra A, Padfield A, Parsons R, Pratt R, Robertson A, Walls S, Wong M, Roughley S  | display-authors = 6 | title = Fatty acid amide hydrolase inhibitors. Surprising selectivity of chiral azetidine ureas | journal = Bioorganic & Medicinal Chemistry Letters | volume = 19 | issue = 15 | pages = 4241–4 | date = August 2009 | pmid = 19515560 | doi = 10.1016/j.bmcl.2009.05.097 }}</ref>
* [[V-158866]] ([[Vernalis plc|Vernalis]]) in clinical trials for neuropathic pain following spinal injury,<ref>{{ClinicalTrialsGov| NCT01748695| A Safety, Tolerability and Efficacy Study of V158866 in Central Neuropathic Pain Following Spinal Cord Injury}}</ref> and spasticity associated with multiple sclerosis. Structure not revealed though Vernalis holds several patents in the area.<ref>{{cite patent | country = US | number = 8450346 | status = granted | title =  Azetidine derivatives as FAAH inhibitors | pubdate = 28 May 2013 | fdate = 27 Feb 2009 | pridate = 4 March 2008 | invent = Roughly S, Walls S, Hart T, Parsons R, Brough P, Graham C, Macias A | assign1 = Vernalis (R&D) Ltd. }}</ref><ref name="pmid22209458">{{cite journal | vauthors = Roughley SD, Browne H, Macias AT, Benwell K, Brooks T, D'Alessandro J, Daniels Z, Dugdale S, Francis G, Gibbons B, Hart T, Haymes T, Kennett G, Lightowler S, Matassova N, Mansell H, Merrett A, Misra A, Padfield A, Parsons R, Pratt R, Robertson A, Simmonite H, Tan K, Walls SB, Wong M | display-authors = 6 | title = Fatty acid amide hydrolase inhibitors. 3: tetra-substituted azetidine ureas with in vivo activity | journal = Bioorganic & Medicinal Chemistry Letters | volume = 22 | issue = 2 | pages = 901–6 | date = January 2012 | pmid = 22209458 | doi = 10.1016/j.bmcl.2011.12.032 }}</ref>
{{Div col end}}

=== Inhibition and binding ===

Structural and conformational properties that contribute to enzyme inhibition and substrate binding imply an extended bound conformation, and a role for the presence, position, and [[stereochemistry]] of a [[Fatty acid#Numbering of the carbon atoms in a fatty acid|delta]] [[Cis–trans isomerism|cis]] [[double bond]].<ref>{{cite journal | vauthors = Boger DL, Sato H, Lerner AE, Austin BJ, Patterson JE, Patricelli MP, Cravatt BF | title = Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: a probe of structural and conformational features contributing to inhibition | journal = Bioorganic & Medicinal Chemistry Letters | volume = 9 | issue = 2 | pages = 265–70 | date = January 1999 | pmid = 10021942 | doi = 10.1016/S0960-894X(98)00734-3 }}</ref>

==Assays==
The enzyme is typically assayed making use of a radiolabelled anandamide [[Substrate (biochemistry)|substrate]], which generates free labelled [[ethanolamine]], although alternative LC-MS methods have also been described.<ref name="pmid20694697">{{cite journal | vauthors = Wang Y, Jones P | title = A scintillation proximity assay for fatty acid amide hydrolase compatible with inhibitor screening | journal = [[Methods in Molecular Biology]] | volume = 572 | issue =  | pages = 247–59 | year = 2009 | pmid = 20694697 | doi = 10.1007/978-1-60761-244-5_16 | series = Methods in Molecular Biology | isbn = 978-1-60761-243-8 }}</ref><ref name="pmid23044255">{{cite journal | vauthors = Han B, Wright R, Kirchhoff AM, Chester JA, Cooper BR, Davisson VJ, Barker E | title = Quantitative LC-MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor | journal = Analytical Biochemistry | volume = 432 | issue = 2 | pages = 74–81 | date = January 2013 | pmid = 23044255 | pmc = 3760509 | doi = 10.1016/j.ab.2012.09.031 }}</ref>

== Structures ==
The first crystal structure of FAAH was published in 2002 ([[Protein Data Bank|PDB]] code 1MT5).<ref name="pmid12459591"/>  Structures of FAAH with drug-like ligands were first reported in 2008, and include non-covalent inhibitor complexes and covalent adducts.<ref name="pmid18753625">{{PDB|2VYA}}; {{cite journal | vauthors = Mileni M, Johnson DS, Wang Z, Everdeen DS, Liimatta M, Pabst B, Bhattacharya K, Nugent RA, Kamtekar S, Cravatt BF, Ahn K, Stevens RC | title = Structure-guided inhibitor design for human FAAH by interspecies active site conversion | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 35 | pages = 12820–4 | date = September 2008 | pmid = 18753625 | pmc = 2529035 | doi = 10.1073/pnas.0806121105 }}</ref>

== See also ==
* [[Endocannabinoid enhancer]]
* [[Endocannabinoid reuptake inhibitor]]
* [[Monoacylglycerol lipase]]
* [[FAAH2]]

== References ==
{{Reflist|33em}}

== External links ==
* {{MeshName|fatty-acid+amide+hydrolase}}
* [http://proteopedia.org/wiki/index.php/2vya Proteopedia FAAH entry] - interactive structure (JMOL) of inhibitor-bound FAAH

{{Cannabinoidergics}}
{{Carbon-nitrogen non-peptide hydrolases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:EC 3.5.1]]
[[Category:Integral membrane proteins]]