CMI-392

CMI-392 (LDP-392) is an orally active dual 5-lipoxygenase inhibitor and platelet-activating factor receptor (PAFR) antagonist, with an IC₅₀ of 10 nM for human PAF receptor and an IC₅₀ of 100 nM for rat 5-lipoxygenase. CMI-392 blocks PAF receptor binding, inhibits leukotriene synthesis, attenuates PAF-induced hemoconcentration, and suppresses arachidonic acid- and TPA-induced ear swelling in mice. CMI-392 reduces inflammatory cell infiltration, decreases MPO levels, alleviates ocular inflammation, and improves dextran sulfate sodium-induced colitis. CMI-392 can be used in the research of inflammatory and immune-related diseases such as colitis and atopic dermatitis^[1][2]. In Vitro:CMI-392 potently inhibits the specific binding of [³H]PAF to cell membranes of CHO cells expressing human PAF receptors, with an IC₅₀ of 10 nM; it inhibits 5-lipoxygenase activity in RBL-2H3 cell extracts, with an IC₅₀ of 100 nM; it suppresses the production of LTB₄ in human whole blood activated by calcium ionophore, with an IC₅₀ of 7.8 μM^[1]. In Vivo:CMI-392 exerts prominent reductions in ear weight, inflammatory cell infiltration and histological inflammatory lesions via topical administration in acute and chronic TPA-triggered ear edema models; presents ED₅₀ values of 2.2 mg/kg and 1.8 mg/kg in PAF-evoked mouse hemoconcentration model and arachidonic acid-stimulated ear edema model, respectively^[1].
CMI-392 (administered orally) dose-dependently alleviates the severity of dextran sulfate sodium (DSS)-induced colitis injury in mice and also inhibits ocular inflammatory responses in a rabbit eye model^[2].