URB597

• 产品号: S2631
• CAS号: 546141-08-6
• 分子式: C20H22N2O3
• 分子量: 338.40028
• 保 存: -20°C

产品别名

• 标题: URB597
• IUPAC标准名: 3-(3-carbamoylphenyl)phenyl N-cyclohexylcarbamate
• IUPAC传统名: 3-(3-carbamoylphenyl)phenyl N-cyclohexylcarbamate
• 别名: KDS-4103

产品登记号

• CAS号: 546141-08-6

产品性质

• 作用靶点: fatty acid amide hydrolase (FAAH)
• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Cancer

Biological Activity

• Description: URB597 (KDS-4103) is a potent FAAH inhibitor with IC50 of 4.6 nM.
• Targets:

  FAAH

• IC50:

  4.6 nM ^[1]

• In Vitro: URB597 binds in the hydrophobic pocket and catalytic core of FAAH that connects the active site residues to the membrane surface of FAAH. ^[1] URB597 inhibits FAAH activity in human liver microsomes with IC50 of 3 nM. ^[2] URB597 reduces the expression of the LPS-induced enzymes cyclo-oxygenase 2 (COX2) 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. ^[3] 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. ^[4]
• In Vivo: 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. ^[5] 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. ^[6] 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. ^[7] URB597 could reverse most depressive-like symptoms induced by adolescent THC exposure in femal rats. ^[8]

Protocol

• Protocol: Kinase Assay ^[1]
• Pharmacology: Membrane fractions are prepared from brain homogenates, and FAAH activity is assayed using [^3H]anandamide (anandamide[ethanolamine-^3H], 60 Ci/mmol) as a substrate. Rat brain membranes (50 μg protein) are incubated for 30 min at 37 °C in buffer containing [^3H]anandamide and varying concentrations of URB597. At the end of the incubation period, we stopp the reactions with a mixture of chloroform/methanol and measured [^3H]ethanolamine in the aqueous phase by liquid scintillation counting.
• Protocol: Animal Study ^[5]
• Animal Models: Adult male Wistar rats (250–300 g) and C57/BL6 or FAAH-/- mice
• Formulation: sterile 0.9% sodium chloride solution
• Doses: 0.3 mg/kg
• Administration: Inject subcutaneously in a single dose 2 hours or 16 hours before killing

References

• References: [1] Mor M, et al. J Med Chem, 2004, 47(21), 4998-5008.
• References: [2] Piomelli D, et al. CNS Drug Rev, 2006, 12(1), 21-38.
• References: [3] Tham CS, et al. FEBS Lett, 2007, 581(16), 2899-2904.
• References: [4] Niforatos W, et al. Mol Pharmacol, 2007, 71(5), 1209-1216.
• References: [5] Fegley D, et al. J Pharmacol Exp Ther, 2005, 313(1), 352-358.
• References: [6] Jayamanne A, et al. Br J Pharmacol, 2006, 147(3), 281-288.
• References: [7] Bortolato M, et al. Biol Psychiatry, 2007, 62(10), 1103-1110.
• References: [8] Realini N, et al. Neuropharmacology, 2011, 60(2-3), 235-243.

参考文献

• Mor M, et al. J Med Chem, 2004, 47(21), 4998-5008.
• Piomelli D, et al. CNS Drug Rev, 2006, 12(1), 21-38.
• Tham CS, et al. FEBS Lett, 2007, 581(16), 2899-2904.
• Niforatos W, et al. Mol Pharmacol, 2007, 71(5), 1209-1216.
• Fegley D, et al. J Pharmacol Exp Ther, 2005, 313(1), 352-358.
• Jayamanne A, et al. Br J Pharmacol, 2006, 147(3), 281-288.
• Bortolato M, et al. Biol Psychiatry, 2007, 62(10), 1103-1110.
• Realini N, et al. Neuropharmacology, 2011, 60(2-3), 235-243.