Prinomastat hydrochloride (C007B-386532)

Prinomastat hydrochloride (AG3340 hydrochloride) is a broad spectrum, potent, orally active metalloproteinase (MMP) inhibitor with IC 50 s of 79, 6.3 and 5.0 nM for MMP-1 , MMP-3 and MMP-9 , respectively. Prinomastat hydrochloride inhibits MMP-2 , MMP-3 and MMP-9 with K i s of 0.05 nM, 0.3 nM and 0.26 nM, respectively. Prinomastat hydrochloride can cross blood-brain barrier. Antitumor avtivity.In VitroPrinomastat (AG3340; 0.1-1 µg/mL; 4 days; C57MG/Wnt1 cells) inhibits Wnt1-induced MMP-3 production. Reversal of Wnt1-induced EMT and β-catenin transcriptional activity by Prinomastat. Co-culture of L/Wnt3a cells and CT7 cells increases the Topflash activity in CT7 cells, and co-culturing both L/Wnt3a cells and MMP-3 overexpressing C57MG cells with CT7 cells increases the Topflash luciferase activity in CT7 cells beyond the level observed with L/Wnt3a cells, and these effects are all suppressed by Prinomastat (AG3340). Inhibition of entry of C57MG/Wnt1 cells into S phase by Prinomastat corresponds to a decrease in expression of cyclin D1 and Erk1/2 phosphorylation. The effect of Prinomastat on Wnt1-induced migration is then examined using an in vitro wound assay. As anticipated, the migration of C57MG/Wnt1 cells is increased by 1.8-fold when compared with C57MG cells.The effect of Wnt1 on the cellular distribution of vimentin is reversed by Prinomastat in C57MG/Wnt1 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: C57MG/Wnt1 cells Concentration: 0.1 µg/mL, 1 µg/mL Incubation Time: 4 days Result: A significant decrease in MMP-3 promoter activity in C57MG/Wnt1 cells.In VivoIn a human fibrosarcoma mouse model (HT1080), the mice are treated therapeutically for 14-16 days with 50 mg/kg/day ip daily starting day 3 to 6 after tumour inoculation. Prinomastat is well tolerated by the animals, and there are no signs of weight loss or other adverse effects. Prinomastat has good tumour growth inhibition, with a short T 1/2 of 1.6 hours . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:Solid.

Molecular Formula: C18H22ClN3O5S2

Molecular Weight: 459.97

PubChem CID: 10321991

Isomeric SMILES: CC1([C@@H](N(CCS1)S(=O)(=O)C2=CC=C(C=C2)OC3=CC=NC=C3)C(=O)NO)C.Cl