URB597

URB597 is a potent, orally bioavailable FAAH inhibitor with IC50 of 4.6 nM, with no activity on other cannabinoid-related targets. Phase 1.

URB597 binds in the hydrophobic pocket and catalytic core of FAAH that connects the active site residues to the membrane surface of FAAH. URB597 inhibits FAAH activity in human liver microsomes with IC50 of 3 nM. URB597 reduces the expression of the LPS-induced enzymes cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS; NOS2) in primary rat microglial cell, with a concomitant reduction in the release of the inflammatory mediators prostaglandin E2 (PGE2) and (NO) nitric oxide. URB597 evokes Ca2+ entry in HEK293-F Cells transiently expressing human or rat TRPA1 gene. URB597 also activates Ca2+ entry in rat DRG neurons natively expressed TRPA1 channels.

URB597 inhibits [3H]anandamide hydrolysis in rat brain membranes with a parallel increase in brain anandamide, OEA, and PEA content by inhibition of FAAH. URB597 enhances the hypothermia effect induced by ethanolamide by inhibiting FAAH.When delivered intraperitonealy (0.3 mg/kg) URB597 reduces allodynia and hyperalgesia through cannabinoid CB1 and CB2 receptor-mediated analgesia in rats with inflammatory pain.URB597 reduces the reduction in body weight gain and sucrose intake induced by the chronic mild stress in rats through inhibition of brain FAAH activity. URB597 could reverse most depressive-like symptoms induced by adolescent THC exposure in femal rats.

URB-597 (546141-08-6) is a potent and selective fatty acid amide hydrolase (FAAH) inhibitor, IC50 = 3-5 nM.1Produces cannabinoid CB1 and CB2 receptor-mediated analgesia in inflammatory pain states without causing side effects associated with cannabinoid receptor activation.2Attenuates the anxiolytic-like effect of acetaminophen in a mouse model.3Exerts anti-inflammatory effects in rat hippocampus and ameliorates age-related deficits.4Off target effects of URB-597: Reduces tyrosine hydroxylase expression.5 Improves cognitiveimpairment caused by chronic cerebral hypoperfusion in a mouse model via inhibition of mTOR-dependent autophagy.6

URB597 is a potent, selective fatty acid amide hydrolase (FAAH) inhibitor.

ChEBI: URB597 is a member of biphenyls.

URB597 binds to active sites of fatty acid amide hydrolases and inhibits their activity. URB597 alters expression of tyrosine hydroxylase and interacts with abnormal-cannabidiol (Abn-CBD) and peroxisome proliferator-activated receptors (PPARs). URB597 elicits antinociception property via cannabinoid receptor by maintaining endocannabinoid anandamide (AEA) levels. URB597 reduces abnormal hyperactivity in neurons and could be for treatment of seizures and improving synaptic plasticity.

Potent, selective fatty acid amide hydrolase (FAAH) inhibitor.

Store at +4°C

[1] DANIELE PIOMELLI. Pharmacological Profile of the Selective FAAH Inhibitor KDS-4103 (URB597)[J]. CNS drug reviews, 2006, 12 1: 21-38. DOI:10.1111/j.1527-3458.2006.00021.x
[2] ANGELO JAYAMANNE. Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models[J]. British Journal of Pharmacology, 2009, 147 3: 281-288. DOI:10.1038/sj.bjp.0706510
[3] SAWSAN A ZAITONE  Soad H A E E  Ahmed F El Wakeil. Inhibition of fatty acid amide hydrolase by URB597 attenuates the anxiolytic-like effect of acetaminophen in the mouse elevated plus-maze test.[J]. Behavioural Pharmacology, 2012, 23 4: 417-425. DOI:10.1097/fbp.0b013e3283566065
[4] NIAMH MURPHY. The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation.[J]. Journal of Neuroinflammation, 2012: 79. DOI:10.1186/1742-2094-9-79
[5] BARBARA BOSIER  Didier M L  Giulio G Muccioli. The FAAH inhibitor URB597 efficiently reduces tyrosine hydroxylase expression through CB1- and FAAH-independent mechanisms[J]. British Journal of Pharmacology, 2012, 169 4: 794-807. DOI:10.1111/j.1476-5381.2012.02208.x
[6] DAPENG WANG . URB597 improves cognitive impairment induced by chronic cerebral hypoperfusion by inhibiting mTOR-dependent autophagy[J]. Neuroscience, 2017, 344: Pages 293-304. DOI:10.1016/j.neuroscience.2016.12.034