GW-405833

GW-405833 (L768242) is a potent, selective cannabinoid receptor 2 (CB₂) agonist. GW405833 has EC₅₀ and K_i values ​​of 0.65 nM and 3.92 nM for CB₂, and EC₅₀ and K_i values ​​of 16.1 μM and 4772 nM for CB₁. GW-405833 also exhibits non-competitive CB₁ antagonist, exerting its analgesic and and anti-inflammatory effect through a CB₁ receptor (rather than CB₂) dependent mechanism. GW-405833 can significantly inhibit the production of cAMP stimulated by Forskolin (HY-15371). GW405833 inhibits glycolysis by down-regulating HIF-1α, thereby alleviating acute liver failure (ALF)^{[1][2][3][4][5]}. In Vitro:GW-405833 behaves as a low-efficacy agonist in spleen membranes from human, mice and rats and exhibits a reverse agonist effect in hCB2-CHO cells^[4].
GW-405833 (10 μM, 25 h) inhibits the proliferation of hepatic macrophages through downregulating HIF-1α to inhibit glycolysis^[5].
In Vivo:GW-405833 (3-30 mg/kg, i.p., single dose) dose-dependently reverses mice mechanical abnormal pain in both neuropathic pain and inflammatory pain models through CB1 receptors rather than CB2 receptors and does not produce typical cannabinoid-like effects^[1].
GW-405833 (3 mg/kg, i.v., single dose) inhibits inflammation and footpad edema of rats by reducing cytokine production and oxidative stress^[3].
GW-405833 (10 mg/kg, i.p., single dose) protects against cell death in acute liver failure (ALF) rats model through downregulating HIF-1α to inhibit glycolysis^[5].