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Inflammatory disease

Leukotriene B4 (LTB4); complement 5 (C5)

In vitro and mouse studies suggest inhibitors of both C5 and LTB4 could help treat inflammatory diseases. In vitro, the tick-derived protein Ornithodoros moubata complement inhibitor (OmCI) bound both LTB4 and C5 and blocked their activation. In a mouse model for antigen-induced acute lung injury, OmCI decreased neutrophil recruitment and damage to pulmonary microvasculature compared with inhibition of Ltb4 or C5 alone. Next steps could include testing OmCI in additional animal models for antigen-induced inflammation.
Cellceutix Corp.'s Kevetrin thioureidobutyronitrile, an LTB4 and protein kinase B (PKB; PKBA; AKT; AKT1) inhibitor, is in Phase I testing to treat solid tumors.
Alexion Pharmaceuticals Inc. markets Soliris eculizumab, a humanized mAb targeting C5, to treat hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria.
At least seven other companies have C5 inhibitors in Phase II testing or earlier to treat various indications.

SciBX 6(24); doi:10.1038/scibx.2013.604
Published online June 20, 2013

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Roversi, P. et al. J. Biol. Chem.; published online April 26, 2013;
Contact: Miles A. Nunn, Centre for Ecology and Hydrology, Wallingford, U.K.