1309040-91-2Relevant academic research and scientific papers
Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs
Nandurdikar, Rahul S.,MacIag, Anna E.,Holland, Ryan J.,Cao, Zhao,Shami, Paul J.,Anderson, Lucy M.,Keefer, Larry K.,Saavedra, Joseph E.
experimental part, p. 3094 - 3099 (2012/06/30)
JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo antitumor activity.
