Prinomastat is a broad spectrum MMP inhibitor with IC50s of 79, 6.3 and 5.0 nM for MMP-1, MMP-3 and MMP-9, respectively.
Co-culture of L/Wnt3a cells and CT7 cells increases the Topflash activity in CT7 cells and this effect is suppressed in the presence of Prinomastat (AG3340). The effect of Wnt1 on the cellular distribution of vimentin is reversed in the presence of Prinomastat in C57MG/Wnt1 cells. Casein gel zymography and western blot analysis of the supernatant of C57MG/Wnt1 cells demonstrate a significant decrease in the presence of MMP-3 in the supernatant of cells treated with Prinomastat or rTIMP-2 that is consistent with these inhibitors inhibiting Wnt1-induced MMP-3 production[3].
Treatment of HaCaT-ras A-5RT3 tumor xenografts with Prinomastat (Ag3340) for 6 days strongly reduces tumor invasion and vascularization. The mean vessel diameter, analyzed by vessel size imaging with MRI, remains constant in untreated animals (day 0: 53±10 μm, day 6: 57±20 μm), but significantly increases in response to Prinomastat treatment (prior to therapy, day 0: 40±10 μm, after therapy, day 6: 70±10 μm; p<0.05). Prinomastat treatment markedly reduces the expression of murine VEGF-A in the stroma of the HaCaT-ras A-5RT3 tumors[2].
[1]. S?rensen MD, et al. Cyclic phosphinamides and phosphonamides, novel series of potent matrix metalloproteinase inhibitors with antitumour activity. Bioorg Med Chem. 2003 Dec 1;11(24):5461-84. [2]. Woenne EC, et al. MMP inhibition blocks fibroblast-dependent skin cancer invasion, reduces vascularization and alters VEGF-A and PDGF-BB expression. Anticancer Res. 2010 Mar;30(3):703-11. [3]. Blavier L, et al. Stromelysin-1 (MMP-3) is a target and a regulator of Wnt1-induced epithelial-mesenchymal transition (EMT). Cancer Biol Ther. 2010 Jul 15;10(2):198-208.