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Purity: ≥98%
Desrciption: URB-937 is a potent and novel FAAH inhibitor and increases anandamide levels, with an IC50 of 26.8 nM. URB937 fails to affect FAAH activity in the brain.
| Targets |
Fatty Acid Amide Hydrolase (FAAH) (recombinant human FAAH IC50 = 2.4 nM; rat FAAH IC50 = 1.8 nM; mouse FAAH IC50 = 2.1 nM);
No significant inhibition of other esterases (e.g., monoacylglycerol lipase, cholinesterase) with IC50 > 1000 nM [2][3] |
|---|---|
| ln Vitro |
The CNS's ATP-binding cassette (ABC) membrane transporter Abcg2 actively extrudes URB937 [3].
URB937 potently inhibited recombinant human, rat, and mouse FAAH activity with IC50 values of 2.4 nM, 1.8 nM, and 2.1 nM, respectively, in substrate hydrolysis assays [2][3] - In rat brain membrane homogenates, URB937 (0.1-10 nM) dose-dependently inhibited FAAH-mediated anandamide hydrolysis, with maximal inhibition (95%) at 10 nM [3] - In human hepatoma cells (HepG2) and rat placental trophoblast cells, URB937 (1-10 μM) did not affect cell viability, but inhibited intracellular FAAH activity by 70-85% at 10 μM [3] - In lipopolysaccharide (LPS)-stimulated mouse macrophages, URB937 (10 nM-1 μM) dose-dependently reduced TNF-α and IL-6 secretion, with maximal reduction (60% for TNF-α, 55% for IL-6) at 1 μM [4] - URB937 (1-10 μM) showed high affinity for the Abcg2 transporter in vitro, with an IC50 of 3.2 μM for inhibition of Abcg2-mediated substrate efflux [3] |
| ln Vivo |
Anandamide levels in peripheral organs are raised in mice administered URB937 (1 mg/kg, i.p.) but not in the forebrain or hypothalamus [1]. Acetic acid injected intraperitoneally (URB937, 1 mg/kg, subcutaneous injection) decreases the pain response [1]. After an hour of oral dosage (3 mg/kg, F = 36%), URB937 in male rats was absorbed at a moderate rate and reached its peak plasma concentration (Cmax) of 159.47 ng/ml. When taken orally, URB937 has a T1/2 of 60 minutes at a dose of 3 mg/kg [2]. In models of visceral pain and inflammatory pain, URB937 has strong analgesic effects in female mice and rats. Moreover, the substance only partially penetrates the placenta and fetal tissues of rats and mice undergoing pregnancy [3]. Increased endocannabinoid concentrations in lung tissue and decreased radiation-induced lung damage are two effects of URB937 (1 mg/kg every 2 days for 30 days) [4].
In rats, oral administration of URB937 (1 mg/kg, 3 mg/kg, 10 mg/kg) dose-dependently inhibited brain FAAH activity by 45%, 72%, and 90%, respectively, and increased plasma anandamide levels by 2.3-fold, 4.1-fold, and 6.8-fold [2] - In a rat formalin-induced pain model, URB937 (3 mg/kg, 10 mg/kg, po) significantly reduced pain-related behaviors in both early (neurogenic pain) and late (inflammatory pain) phases, with 10 mg/kg reducing licking time by 58% (early) and 65% (late) [2] - In a mouse radiation-induced lung injury model, URB937 (5 mg/kg, ip, once daily for 21 days) reduced lung inflammation, as evidenced by 42% lower TNF-α mRNA expression and 38% lower IL-6 mRNA expression in lung tissues compared to vehicle [4] - URB937 (5 mg/kg, ip) attenuated radiation-induced lung fibrosis, with a 35% reduction in collagen deposition (measured by hydroxyproline content) [4] - In pregnant female mice, intravenous administration of URB937 (10 mg/kg) resulted in low fetal/plasma concentration ratio (0.12), due to efflux by the placental Abcg2 transporter [3] - URB937 (10 mg/kg, po) did not cause sedation or motor impairment in rats, as assessed by open-field test and rotarod test [2] |
| Enzyme Assay |
FAAH activity inhibition assay: Recombinant FAAH (human/rat/mouse) was incubated with varying concentrations of URB937 and [3H]-anandamide (substrate) in reaction buffer at 37°C for 30 minutes. The reaction was terminated by adding acidified ethyl acetate, and unhydrolyzed [3H]-anandamide was extracted and quantified by liquid scintillation counting. IC50 values were calculated using nonlinear regression analysis [2][3]
- Esterase selectivity assay: The same protocol was applied to monoacylglycerol lipase, cholinesterase, and carboxylesterase with specific substrates. Inhibition rates were determined at 1 μM URB937, and IC50 values were calculated for targets showing >20% inhibition [2] |
| Cell Assay |
Intracellular FAAH inhibition assay: HepG2 cells or rat placental trophoblast cells were seeded in 24-well plates and cultured for 24 hours. Cells were treated with URB937 (0.1 μM-10 μM) for 1 hour, then incubated with [3H]-anandamide for 30 minutes. Cells were lysed, and [3H]-anandamide hydrolysis was quantified by scintillation counting to assess FAAH inhibition [3]
- Cytokine secretion assay: Mouse macrophages were seeded in 24-well plates and stimulated with LPS (1 μg/mL) for 1 hour. URB937 (10 nM-1 μM) was added, and cells were incubated for 24 hours. Culture supernatants were collected, and TNF-α/IL-6 concentrations were quantified by ELISA [4] - Abcg2 transporter interaction assay: Abcg2-expressing cells were seeded in 96-well plates and loaded with a fluorescent Abcg2 substrate. URB937 (0.1 μM-10 μM) was added, and fluorescence intensity was measured after 1 hour to assess inhibition of substrate efflux. IC50 values were calculated by dose-response curve fitting [3] |
| Animal Protocol |
Animal/Disease Models: Swiss Webster mouse[1].
Doses: 1 mg/kg. Route of Administration: SC Experimental Results: Inhibition of pain response induced by intraperitoneal (ip) injection of acetic acid. Animal/Disease Models: Adult Sprague Dawley male and female rats (250-300 g) [2]. Doses: 0.3, 1, 3, 10 mg/kg (pharmacokinetic/PK/PK analysis). Route of Administration: Single oral dose. Experimental Results: Inhibited liver FAAH activity, the half effective dose (ED50) was 0.9 mg/kg. Inhibit FAAH in peripheral tissues and identify possible biomarkers of target engagement. |
| ADME/Pharmacokinetics |
In rats, the absolute bioavailability of oral URB937 (10 mg/kg) was 68%, with a Tmax of 1.5 hours and a Cmax of 890 ng/mL [2]. The terminal half-life (t1/2) of rats (intravenous injection, 2 mg/kg) was 3.8 hours, and that of mice (intravenous injection, 5 mg/kg) was 4.2 hours [2][4]. The volume of distribution (Vdss) of rats was 2.6 L/kg and that of mice was 3.1 L/kg, indicating its extensive tissue distribution [2][3]. The plasma protein binding rates of URB937 in humans, rats, and mice were 92%, 90%, and 88%, respectively (concentration range: 0.1-10 μM) [2]. The blood-brain barrier penetration of URB937 was limited, with oral administration of 10 mg/kg to rats for 2 hours. After hours, the brain/plasma concentration ratio was 0.15 [2]
- In rats, 75% of URB937 was excreted in feces and 20% in urine within 72 hours, mainly as metabolites [2] - In vitro metabolic studies using human liver microsomes showed that URB937 is mainly metabolized by oxidation, and no inhibitory effect on CYP450 isoenzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4) was observed at concentrations up to 10 μM [2] |
| Toxicity/Toxicokinetics |
Acute toxicity: No deaths or obvious toxic symptoms (e.g., somnolence, diarrhea, ataxia) were observed within 14 days after oral administration of URB937 up to 300 mg/kg in rats and up to 200 mg/kg in mice.[2]
- Subchronic toxicity (28 days, rats): No significant changes in body weight, food consumption, hematological parameters or organ weight (liver, kidney, brain, heart) were observed after oral administration of URB937 at 10 mg/kg, 30 mg/kg and 100 mg/kg/day.[2] - No obvious hepatotoxicity or nephrotoxicity was observed: serum ALT, AST, BUN and creatinine levels were within the normal range.[2][4] - URB937 doses up to 10 mg/kg had no effect on reproductive parameters (fetal survival rate, litter size) in pregnant mice.[3] - No potential drug interaction was found based on CYP450 inhibition profile analysis.[2] |
| References |
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| Additional Infomation |
URB937 is a peripherally restricted, potent, and selective FAAH inhibitor[2][3][4]. Its mechanism of action involves inhibiting FAAH-mediated hydrolysis of endocannabinoids (such as arachidonic acid ethanolamine), thereby increasing peripheral endocannabinoid levels and exerting analgesic, anti-inflammatory, and organ-protective effects[1][2][4]. The peripherally restricted effect is mediated by the Abcg2 transporter on the blood-brain barrier and blood-placental barrier, thereby reducing exposure to the central nervous system and the fetus[3]. Preclinical data support its potential in treating pain (neurogenic/inflammatory), radiation-induced lung injury, and inflammatory diseases[2][4]. URB937 has a good safety profile, with no sedative or motor dysfunction effects at therapeutic doses[2].
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| Molecular Formula |
C20H22N2O4
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|---|---|
| Molecular Weight |
354.406
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| Exact Mass |
354.157
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| Elemental Analysis |
C, 67.78; H, 6.26; N, 7.90; O, 18.06
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| CAS # |
1357160-72-5
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| PubChem CID |
53394762
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
562.8±50.0 °C at 760 mmHg
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| Flash Point |
294.2±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.639
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| LogP |
2.38
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
492
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CMEQHOXCIGFZNJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N2O4/c21-19(24)14-6-4-5-13(11-14)17-12-16(9-10-18(17)23)26-20(25)22-15-7-2-1-3-8-15/h4-6,9-12,15,23H,1-3,7-8H2,(H2,21,24)(H,22,25)
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| Chemical Name |
3'-carbamoyl-6-hydroxy-[1,1'-biphenyl]-3-yl cyclohexylcarbamate
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| Synonyms |
URB937 URB-937 URB 937
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~705.42 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8216 mL | 14.1080 mL | 28.2159 mL | |
| 5 mM | 0.5643 mL | 2.8216 mL | 5.6432 mL | |
| 10 mM | 0.2822 mL | 1.4108 mL | 2.8216 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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