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Amifostine thiol (WR-1065) is an active metabolite of the cytoprotector Amifostine . Amifostine thiol is a cytoprotective agent with radioprotective abilities. Amifostine thiol activates p53 through a JNK-dependent signaling pathway[1][2][3].

Amifostine thiol can reduce both the direct and delayed detrimental effects of both high and low-LET radiation exposures[1].Amifostine thiol attenuates both the DNA damage and the G1-phase arrest induced by radiation[1].Amifostine thiol (4 mM; 30 minutes) protects RKO36 cells from chromosomal damage and death induced by ionizing radiation[1].Amifostine thiol (4 mM; 30 minutes) protects irradiated RKO36 cells from delayed genomic instability[1].Amifostine thiol is cytotoxic to RKO36 cells at milimolar concentrations, especially after continuous treatment[1].Amifostine thiol at 40 μM protects RKO36 cells from delayed genomic instability but not from cell death and immediate chromosomal damage[1].Amifostine thiol activates JNK resulting in the phosphorylation of p53 at threonine 81[2].Amifostine thiol affects phosphorylation of topoisomerase IIα leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells[3].

[1]. Jaroslaw Dziegielewski, et al. WR-1065, the Active Metabolite of Amifostine, Mitigates Radiation-Induced Delayed Genomic Instability. Free Radic Biol Med. 2008 Dec 15; 45(12): 1674-1681. [2]. Olivier Pluquet, 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. J Biol Chem. 2003 Apr 4;278(14):11879-87. [3]. J. S. Murley, et al. WR-1065, an active metabolite of the cytoprotector amifostine, affects phosphorylation of topoisomerase IIα leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells. Cell Prolif. 1997 Jun; 30(6): 283-294.

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