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HU-308 is a selective agonist of CB2-receptor with a Ki value of 20 nM. The Ki value for CB1-receptor is >10 µM. Cannabinoid 2 receptor (CB2-receptor) belongs to the seven transmembranes G protein-coupled receptor superfamily. It is mainly distributed in peripheral tissue associated with immune functions.In HLSECs, HU-308 markedly reduced the expression of both ICAM-1 and VCAM-1, which was induced by TNFα. HU-308 attenuated TNF- treatment induced RhoA activation (4.0-fold vs. control) and NF-B Activation. HU-308 inhibited TNFα-induced monocyte adhesion in aortas ex vivo [1].HU-308 increased both primary neurosphere generation and neural progenitor self-renewal. HU-308 increased the number of BrdU incorporating cells in a CB2-dependent manner. HU-308 stimulated ERK and Akt [2].Pretreatment of mice with HU-308 decreases the I/R-induced tissue damage, inflammatory cell infiltration, tissue and serum TNF-α, MIP-1, and MIP-2 levels, tissue lipid peroxidation and apoptosis [3].References: 1.Rajesh M, Mukhopadhyay P, Bátkai S, et al. CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion. Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2210-8.2.Palazuelos J, Aguado T, Egia A, et al. Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation. FASEB J. 2006 Nov;20(13):2405-7. 3.Rajesh M, Pan H, Mukhopadhyay P, et al. Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis. J Leukoc Biol. 2007 Dec;82(6):1382-9.
Cell lines
Human liver sinusoidal endothelial cells (HLSECs); human coronary artery endothelial cells (HCAECs)
Preparation method
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions
HLSECs:0–4 μM for 4 h; HCSECs:3 μM for 4 h
Applications
In HCSECs or HLSECs, HU-308 treatment reduced the expression of both ICAM-1 and VCAM-1, which was induced by TNFα. HU-308 attenuated TNFα treatment induced RhoA activation (4.0-fold vs. control) and NF-B Activation. HU-308 inhibited TNFα-induced monocyte adhesion in aortas.
Animal models
C57Bl/6J mice
Dosage form
HU-308 (10 mg/kg) was injected into the femoral vein right before the reocclusion.
Pretreatment of mice with HU-308 decreases the I/R-induced tissue damage, inflammatory cell infiltration, tissue and serum TNF-α, MIP-1, and MIP-2 levels, tissue lipid peroxidation and apoptosis.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1]. Rajesh M, Mukhopadhyay P, Bátkai S, et al. CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion. Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2210-8.
[2]. Rajesh M, Pan H, Mukhopadhyay P, et al. Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis. J Leukoc Biol. 2007 Dec;82(6):1382-9.