Alagebrium bromide  (Synonyms: ALT711 bromide)

Alagebrium bromide is a cross-link breaker. This study investigated the role of advanced glycation end products (AGEs) in mediating protein kinase C (PKC) isoform expression in diabetic nephropathy. In vitro, vascular smooth muscle cells cultured in high glucose (25-mmol/l) showed increased translocation and expression of PKC-α compared with cells cultured in low glucose (5-mmol/l). Coculture with ALT-711 more effectively attenuated the increased expression and translocation of PKC-α compared with aminoguanidine, an inhibitor of AGE formation. Streptozotocin-induced diabetic rats were randomized to no treatment, ALT-711 treatment, or aminoguanidine treatment. Diabetes induced an increase in PKC-α as well as -βI, -βII, and -ε isoforms. ALT-711 and aminoguanidine treatment, both of which attenuated renal AGE accumulation, abolished these increases in PKC expression. However, only ALT-711 reduced the translocation of phosphorylated PKC-α from the cytoplasm to the membrane. ALT-711 treatment attenuated the expression of vascular endothelial growth factor (VEGF) and extracellular matrix proteins (fibronectin and laminin) and was associated with a reduction in albuminuria. Aminoguanidine had no effect on VEGF expression, although a reduction in fibronectin and laminin was observed. These findings suggest that AGEs are important stimulators of PKC activation, particularly PKC-α, in patients with diabetic nephropathy, which can be directly inhibited by ALT-711.

312.23

C₁₃H₁₄BrNOS

181069-80-7

O=C(C1=CC=CC=C1)C[N+]2=CSC(C)=C2C.[Br-]

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Attenuation of Extracellular Matrix Accumulation in Diabetic Nephropathy by the Advanced Glycation End Product Cross-Link Breaker ALT-711 via a Protein Kinase C-α−Dependent Pathway