CGP-43182

CGP-43182 is a secretory phospholipase A2 group II (sPLA2) inhibitor with an IC₅₀ of 2.8 μM. CGP-43182 binds to the active site of the enzyme, blocks IL1β-stimulated gene expression and NFκB activation, and inhibits the production of prostaglandin and nitric oxide (NO). CGP-43182 exhibits anti-inflammatory activity in multiple inflammatory models and can be used for studies on adjuvant arthritis, carrageenan-induced edema, pertussis pleurisy, and glomerular inflammatory responses^[1][2][3][4]. In Vitro:CGP-43182 potently and selectively inhibits purified group IIA sPLA₂ with an IC₅₀ of 2.8 μM, exhibits much weaker activity against group IB sPLA₂, and shows no activity against cytosolic PLA₂^[1].
CGP-43182 (1-10 μM; 30 min pre-incubation, 24 h co-incubation) potently inhibits IL-1β-induced group IIA sPLA₂ mRNA expression, protein secretion and enzyme activity in rat renal mesangial cells (complete inhibition at 5 μM), but does not affect the db-cAMP-stimulated group IIA sPLA₂ response ^[1].
CGP-43182 (1-10 μM; 24 h) potently inhibits IL-1β-induced Cox-2 mRNA expression and prostacyclin production in rat glomerular mesangial cells (complete inhibition at 5 μM), but does not affect the db-cAMP-stimulated Cox-2 response^[1].
CGP-43182 (0.1-30 μM; 30 min-1 h) potently and selectively inhibits secretory phospholipase A₂ type II secreted by rat mesangial cells, while exerting only an extremely weak effect on the activity of cytosolic phospholipase A₂ in rat mesangial cells^[2].
CGP-43182 (3-10 μM; 24 h) potently inhibits IL-1β-induced iNOS mRNA expression and nitrite production in rat renal mesangial cells (complete inhibition at 5 μM), but does not affect the db-cAMP-stimulated iNOS response^[1].
CGP-43182 (10 μM; 30 min) completely blocks the DNA-binding activity of NFκB in IL-1β-stimulated rat renal mesangial cells at a concentration of 10 μM^[1].
CGP-43182 (1-10 μM; 15 min) interferes with IL-1β-induced phosphorylation and degradation of IκBα in rat renal mesangial cells, with significant effects observed at concentrations of 5 μM and 10 μM^[1].
CGP-43182 (24 h) potently inhibits IL-1β- and TNFα-stimulated PGE₂ synthesis in rat mesangial cells, with IC₅₀ values of 1.3 μM and 1.0 μM, respectively^[2].
CGP-43182 (10 μM; 30 min) completely blocks the arachidonic acid-releasing activity of purified group II sPLA₂ from rat mesangial cells in rat mesangial cells ^[2].
CGP-43182 (0.1-10 μM; 24 h) potently inhibits IL-1β- and TNFα-stimulated PGE₂ synthesis in rat mesangial cells, with IC₅₀ values of 1.3 μM and 1.0 μM, respectively; at a concentration of 10 μM, it suppresses approximately 70% of cytokine-induced PGE₂ production^[3].
CGP-43182 (5-80 μM; 15 min pretreatment) does not inhibit 60 mM Sodium Fluoride (NaF) (HY-B1766)-induced [³H]-arachidonic acid release in bovine aortic endothelial cells, even at concentrations as high as 80 μM ^[4]. In Vivo:CGP-43182 exhibits anti-inflammatory activity in the pertussis pleurisy in vivo model by reducing exudate volume, cell infiltration, and eicosanoid production^[1].
CGP-43182 displays anti-inflammatory activity in the adjuvant arthritis in vivo model^[1].
CGP-43182 demonstrates anti-inflammatory activity in the carrageenan-induced oedema in vivo model^[1].