EX-597

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| verifiedrevid = 470619330

| Verifiedfields = changed

| Watchedfields = changed

| image = URB597.svg

| width =

| pronounce =

| tradename =

| Drugs.com =

| MedlinePlus =

| licence_CA =

| licence_EU =

| DailyMedID =

| licence_US =

| pregnancy_AU =

| pregnancy_category =

| dependency_liability =

| addiction_liability =

| routes_of_administration =

| class =

| ATC_prefix =

| ATC_suffix =

| legal_status =

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 546141-08-6

| CAS_supplemental =

| PubChem = 1383884

| IUPHAR_ligand = 4339

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 1156960

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = PX47LB88FO

| KEGG =

| ChEBI = 188061

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 184238

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = URB597; URB-597; KDS-4103; ORG-231295

| IUPAC_name = [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate

| C=20 | H=22 | N=2 | O=3

| SMILES = C1CCC(CC1)NC(=O)OC2=CC=CC(=C2)C3=CC(=CC=C3)C(=O)N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C20H22N2O3/c21-19(23)16-8-4-6-14(12-16)15-7-5-11-18(13-15)25-20(24)22-17-9-2-1-3-10-17/h4-8,11-13,17H,1-3,9-10H2,(H2,21,23)(H,22,24)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = ROFVXGGUISEHAM-UHFFFAOYSA-N

}}

EX-597 (former developmental code names URB-597, KDS-4103, and ORG-231295) is a fatty acid amide hydrolase inhibitor (FAAH inhibitor){{cite journal | vauthors = Piomelli D, Tarzia G, Duranti A, Tontini A, Mor M, Compton TR, Dasse O, Monaghan EP, Parrott JA, Putman D | title = Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597) | journal = CNS Drug Reviews | volume = 12 | issue = 1 | pages = 21–38 | date = 2006 | pmid = 16834756 | pmc = 6741741 | doi = 10.1111/j.1527-3458.2006.00021.x }}

which is under development for the treatment of social anxiety disorder (or social phobia) and post-traumatic stress disorder (PTSD).{{cite web | title=EX 597 | work = AdisInsight | publisher = Springer Nature Switzerland AG | date=28 November 2023 | url=https://adisinsight.springer.com/drugs/800022923 | access-date=6 August 2024}}

It is a relatively selective and irreversible inhibitor of the enzyme fatty acid amide hydrolase (FAAH).{{cite journal | vauthors = Mor M, Rivara S, Lodola A, Plazzi PV, Tarzia G, Duranti A, Tontini A, Piersanti G, Kathuria S, Piomelli D | title = Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 21 | pages = 4998–5008 | date = October 2004 | pmid = 15456244 | doi = 10.1021/jm031140x | s2cid = 43473180 }}{{cite journal | vauthors = Alexander JP, Cravatt BF | title = Mechanism of carbamate inactivation of FAAH: implications for the design of covalent inhibitors and in vivo functional probes for enzymes | journal = Chemistry & Biology | volume = 12 | issue = 11 | pages = 1179–1187 | date = November 2005 | pmid = 16298297 | pmc = 1994809 | doi = 10.1016/j.chembiol.2005.08.011 }} FAAH is the primary degradatory enzyme for the endocannabinoid anandamide and, as such, inhibition of FAAH leads to an accumulation of anandamide in the CNS and periphery where it activates cannabinoid receptors. EX-597 has been found to elevate anandamide levels and have activity against neuropathic pain in a mouse model.{{cite journal | vauthors = Russo R, Loverme J, La Rana G, Compton TR, Parrott J, Duranti A, Tontini A, Mor M, Tarzia G, Calignano A, Piomelli D | title = The fatty acid amide hydrolase inhibitor URB597 (cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester) reduces neuropathic pain after oral administration in mice | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 322 | issue = 1 | pages = 236–242 | date = July 2007 | pmid = 17412883 | doi = 10.1124/jpet.107.119941 | s2cid = 40603248 }}

Preclinical studies have shown FAAH inhibitors to increase brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex,{{cite journal | vauthors = Bambico FR, Duranti A, Nobrega JN, Gobbi G | title = The fatty acid amide hydrolase inhibitor URB597 modulates serotonin-dependent emotional behaviour, and serotonin1A and serotonin2A/C activity in the hippocampus | journal = European Neuropsychopharmacology | volume = 26 | issue = 3 | pages = 578–590 | date = March 2016 | pmid = 26747370 | doi = 10.1016/j.euroneuro.2015.12.027 | hdl-access = free | s2cid = 45109526 | hdl = 11576/2631931 }} highlighting their potential in addiction treatment as "enviromimetics".{{cite journal | vauthors = Solinas M, Chauvet C, Lafay-Chebassier C, Jaafari N, Thiriet N | title = Environmental enrichment-inspired pharmacological tools for the treatment of addiction | journal = Current Opinion in Pharmacology | volume = 56 | pages = 22–28 | date = February 2021 | pmid = 32966941 | doi = 10.1016/j.coph.2020.09.001 | s2cid = 221888359 | doi-access = free }} Indeed, Chauvet et al. found that chronic EX-597 administration in rats "significantly reduces cocaine-seeking behaviour and cue- and stress-induced relapse".{{cite journal | vauthors = Chauvet C, Nicolas C, Thiriet N, Lardeux MV, Duranti A, Solinas M | title = Chronic stimulation of the tone of endogenous anandamide reduces cue- and stress-induced relapse in rats | journal = The International Journal of Neuropsychopharmacology | volume = 18 | issue = 1 | pages = pyu025 | date = December 2014 | pmid = 25522382 | pmc = 4368869 | doi = 10.1093/ijnp/pyu025 }}

EX-597 was at one point being developed by Kadmus Pharmaceuticals, Inc. for clinical trials in humans.{{cite web | url = http://www.kadmuspharma.com/ | title = Kadmus Pharmaceuticals | archive-url=https://web.archive.org/web/20051219040657/http://www.kadmuspharma.com/ | archive-date = 19 December 2005 }}