Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor.

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Qian C, Hwang SB, Libertine-Garahan L, Eckman JB, Cai X, Scannell RT, Yeh CG

Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor.

Pharmacol Res. 2001 Sep;44(3):213-20.

PubMed ID

11529688 [ View in PubMed

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Abstract

Leukotrienes (LTs) and platelet-activating factor (PAF) are important mediators of inflammation and allergy. LDP-392, a novel dual PAF receptor antagonist and 5-lipoxygenase (5-LO) inhibitor, has been identified. LDP-392 is 17.9-fold more potent than zileuton (5-LO inhibitor) in the RBL cytosolic 5-LO assay, and equally potent as MK 287 (PAF receptor antagonist) in the human platelet PAF receptor binding assay. The in vivo dual activities of LDP-392 were confirmed by measuring the inhibition of ex vivo LTB(4)production in rats and PAF-induced hemoconcentration in mice. Intravenous administration of LDP-392 demonstrated greater inhibition than zileuton, BN 50739 or MK 287 on arachidonic acid-induced ear edema and protected mice from LPS-induced lethality. Topical administration of LDP-392, in a dose-dependent manner, inhibited TPA-induced ear edema in mice and UVB-induced erythema in guinea-pigs. These data suggest that LDP-392, as a dual PAF receptor antagonist and 5-LO inhibitor, may be of greater clinical effectiveness.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Platelet Activating Factor	Platelet-activating factor receptor	Protein	Humans	Unknown	Not Available	Details
Zileuton	Arachidonate 5-lipoxygenase	Protein	Humans	Yes	Inhibitor	Details