Gevokizumab

Gevokizumab is a potent anti-IL-1β antibody, negatively modulates IL-1β signaling through an allosteric mechanism. Gevokizumab selectively decreases the binding affinity of IL-1β for the IL-1 receptor type I (IL-1RI) signaling receptor instead of IL-1 counter-regulatory decoy receptor (IL-1 receptor type II)[1][2].

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

Research Areas >> Inflammation/Immunology

Gevokizumab (5 nM; 16 h) shows inhibitory effects of IL-1β-mediated NF-kB activation caused by the soluble receptors, sIL-1RI and sIL-1RII in HeLa cells[1]. Gevokizumab (1.85, 5.55, 16.66, and 50 nM) is a selective negative allosteric modulator which reduces the binding affinity of sIL-1RI to IL-1β[1].

Gevokizumab (1 mg/kg; i.v.; once daily for 3 d) improves endothelial regrowth and reduces neointima formation in rats following carotid denudation[2]. Animal Model: Rat carotid denudation model in Sprague-Dawley rats (3-month0-old, 330-360 g)[2] Dosage: 1, 10 and 50 mg/kg Administration: Intravenous injection; once daily for 3 days Result: Decreased carotid intima-media thickness (IMT) in the proximal part of the denuded artery at day 28, and improved endothelial regrowth at 1 mg/kg. 

[1]. Issafras H, et al. Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1β antibody with differential receptor-modulating properties. J Pharmacol Exp Ther. 2014 Jan;348(1):202-15. 

[2]. Roubille F, et al. The interleukin-1β modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model. Atherosclerosis. 2014 Oct;236(2):277-85.