STRUCTURAL-BASED INHIBITORS OF THE GLUTATHIONE BINDING SITE IN ALDOSE REDUCTASE, METHODS OF SCREENING THEREFOR AND METHODS OF USE

摘要

Provided herein are methods of treating a pathophysiological state or symptoms thereof resulting from aldose reductase-mediated signaling in a cytotoxic pathway in a subject using an inhibitor of aldose reductase. Particularly, specific inhibitors may be a small- interfering RNA (siRNA) or may be inhibitors of glutathi one-aldehyde binding to aldose reductase which are designed via at least computer modeling of the ternary A R: NA DPH: DCEG structure. Also, methods of treating a cancer or suppressing metastasis thereof using the siRNAs and aldose reductase inhibitors are provided.