wr-1065

WR-1065 is a small molecule aminothiol compound, specifically the dephosphorylated active metabolite of amifostine (Ethyol)[2][4][5]. As a cytoprotective agent, WR-1065 exhibits antioxidant and reductant properties, notably scavenging reactive oxygen species and participating in polyamine-mediated reactions. Its primary mechanism is protection of normal tissues against damage from ionizing radiation or certain chemotherapeutics by reducing DNA damage and stabilizing cellular genome[2][4][5]. WR-1065 activates the p53 protein by preventing proteasomal degradation, enhancing nuclear p53 levels, and restoring the function of some mutant p53 proteins[1][5]. It induces downstream cell cycle arrest genes (e.g., p21), apoptosis regulators (e.g., Bax-1, Fas), and boosts antioxidant enzymes such as manganese superoxide dismutase (MnSOD)[1][4]. WR-1065 may inhibit topoisomerase IIα and subsequently slow cell growth[4][5]. It can sensitize some tumor cells to chemotherapy and reverse some types of drug resistance, with additional preclinical evidence for anticancer effects, modulation of angiogenesis, and antiviral activity[1][3][5]. WR-1065 itself does not have well-characterized direct clinical use, but is under investigation as a prodrug and in formulations for improved intracellular delivery in oncology and radioprotection applications, including for astronauts and accidental radiation exposure[1][3][4][5].

Other names

2-(3-aminopropylamino)ethanethiol dihydrochlorideactive metabolite of amifostineCAS 14653-77-1CAS14653-77-1CAS-14653-77-1