WR-1065 dihydrochloride

WR-1065 dihydrochloride can protect normal tissues from the toxic effects of certain cancer drugs and activate p53 through a JNK-dependent signaling pathway.

The DNA-binding activity is increased in a WR-1065 dihydrochloride (WR-1065) concentration-dependent manner. Cells treated with 1 mM WR-1065 dihydrochloride for 24 h reveal that all of the p53-induced genes analyzed are transactivated following WR-1065 dihydrochloride treatment, in a p53-dependent manner. Significantly, treatment with WR-1065 dihydrochloride leads to a 3-fold increase in luciferase expression driven by AP-1, and a 5-fold increase when this reporter gene is driven by NF-κB, when these values are normalized to the level of the cotransfected β-galactosidase gene[2].

The results show that wR-1065 dihydrochloride (WR-1065) attenuates the severity of 6-OHDA-induced catalepsy (P<0.001) when compare with 6-OHDA-lesioned rats. Also it has been observed that WR-1065 dihydrochloride improves catalepsy in dose dependent manner (P<0.001). Pretreatment with three different doses of WR-1065 dihydrochloride (20, 40 and 80 μg/2 μL/rat) for 3 days before 6-OHDA administration, significantly (P<0.001) elevates SOD activity and restores it to normal range compare with 6-OHDA lesioned rats[3].

Reference:
[1]. Pluquet O, et al. The cytoprotective aminothiol WR1065 activates p53 through a non-genotoxic signaling pathway involving c-Jun N-terminal kinase. J Biol Chem. 2003 Apr 4;278(14):11879-87.
[2]. Shen H, et al. Binding of the aminothiol WR-1065 to transcription factors influences cellular response to anticancer drugs. J Pharmacol Exp Ther. 2001 Jun;297(3):1067-73.
[3]. Afshin Kheradmand, et al. Effect of WR-1065 on 6-hydroxydopamine-induced catalepsy and IL-6 level in rats. Iran J Basic Med Sci. 2016 May; 19(5): 490-496.