Allo-aca, a leptin peptidomimetic, is a potent, specific leptin receptor antagonist peptide. Allo-aca blocks leptin signaling and action in numerous in vitro and in vivo models[1][2].
Allo-aca inhibits leptin-induced proliferation of MDA-MB-231 cells at 50 pM concentration. Allo-aca inhibits leptin-induced proliferation of MCF-7 cells with an IC50 of 200 pM[1].Allo-aca at 250 nmol/L reduces VEGF-dependent leptin mRNA expression in both cell lines below base levels. Allo-aca inhibits VEGF mitogenic effects. Allo-aca inhibits VEGF-induced chemotaxis and chemokinesis in RF/6A retinal endothelial cells[2].
In an MDA-MB-231 orthotopic mouse xenograft model, Allo-aca administered subcutaneously significantly extends the average survival time from 15.4 days (untreated controls) to 24 and 28.1 days at 0.1 and 1mg/kg/day doses, respectively[1].
[1]. Otvos L Jr, et al. Efficacy of a leptin receptor antagonist peptide in a mouse model of triple-negative breast cancer. Eur J Cancer. 2011;47(10):1578-1584.
[2]. Coroniti R, et al. Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects in Ophthalmic Neoangiogenesis Models [published correction appears in Front Mol Biosci. 2016 Nov 18;3:75]. Front Mol Biosci. 2016;3:67. Published 2016 Oct 13.