6-(4-Fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo[2,1-b]thiazole dihydrochloride

Description

SKF 86002 is an anti-inflammatory agent. It inhibits rat seminal vesicle prostaglandin H₂ (PGH₂) synthase (IC₅₀ = 120 μM), as well as prostanoid production by rat basophilic leukemia (RBL-1) cells and human monocytes (IC₅₀s = 70 and 1 μM, respectively). SKF 86002 inhibits leukotriene B₄ (LTB₄) and LTC₄ production induced by A23187 in human neutrophils and monocytes, respectively (IC₅₀ = 20 μM for both). It also inhibits LPS-induced IL-1 production in human monocytes (IC₅₀ = 1.3 μM). SKF 86002 (10, 30, and 90 mg/kg) reduces hindleg volume in rat models of adjuvant- or collagen-induced arthritis. It also decreases serum levels of TNF-α and increases survival in a mouse model of LPS and galactosamine-induced endotoxic shock when administered at a dose of 100 mg/kg.

Uses

SKF 86002 is an inhibitor of p53, Cox, and 5-LO.

Definition

ChEBI: 6-(4-fluorophenyl)-5-pyridin-4-yl-2,3-dihydroimidazo[2,1-b]thiazole is a member of imidazoles.

Biological Activity

Inhibitor of p38 MAP kinase (IC 50 = 0.1-1 μ M). Potently inhibits LPS-induced IL-1 and TNF- α production in human monocytes (IC 50 = 1 μ M). Also inhibits 5-lipoxygenase- and cyclooxygenase-mediated arachidonic acid metabolism in RBL-1 cells (IC 50 values are 10 and 100 μ M respectively). Anti-inflammatory following oral administration in vivo .

in vivo

References

[1] DON E. GRISWOLD. SK&F 86002: A structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid[J]. Biochemical pharmacology, 1987, 36 20: Pages 3463-3470. DOI: 10.1016/0006-2952(87)90327-3
[2] JOHN C. LEE. Inhibition of monocyte IL-1 production by the anti-inflammatory compound, SK&F 86002[J]. International journal of immunopharmacology, 1988, 10 7: Pages 835-843. DOI: 10.1016/0192-0561(88)90007-0
[3] M J DIMARTINO. Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase.[J]. Agents and Actions, 1987, 20 1-2: 113-123. DOI: 10.1007/bf01965633
[4] A M BADGER. Protective effect of SK&F 86002, a novel dual inhibitor of arachidonic acid metabolism, in murine models of endotoxin shock: inhibition of tumor necrosis factor as a possible mechanism of action.[J]. Circulatory shock, 1989, 27 1: 51-61.