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It is typically characterized by the (15;17) chromosomal translocation, producing the pathogenic retinoic acid receptor (RAR) alpha\/promyelocytic leukemia (PML) fusion protein. Recently, remission of APL has been achieved using the first chemotherapy\u2010independent oral drug regimen in anticancer therapy, consisting of all\u2010trans retinoic acid (targeting RARalpha) and the arsenic sulfide realgar (targeting PML). However, clinical adoption of realgar and the characterization of its active breakdown products have been hampered by its poor solubility. Here, a scalable pH\/temperature\u2010based process is described that partially mimics gut transition, achieving fast and reproducible solubilization of realgar. Six different spectroscopic and spectrometric techniques are employed to investigate solubilized realgar. Furthermore, it is shown that solubilized realgar targets PML, displaying wider in vitro therapeutic indices and lower off\u2010target effects than arsenic trioxide, the current APL standard of care. Moreover, in line with evidence of an interplay between PML and HIV persistence, solubilized realgar can disrupt HIV latency, the main barrier to an HIV\/AIDS cure, in CD4 T cells of people living with HIV. These findings may open avenues for streamlining realgar solubilization and designing less toxic, orally administrable arsenic\u2010based therapies.<\/jats:p>","DOI":"10.1002\/advs.202502740","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:31:22Z","timestamp":1745476282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fast pH\u2010Driven Solubilization Method of Realgar (As\n                    <sub>4<\/sub>\n                    S\n                    <sub>4<\/sub>\n                    ) to Reduce the Toxicity of Arsenic [As(III)] for Medicinal Purposes"],"prefix":"10.1002","volume":"12","author":[{"given":"Bojana","family":"Lucic","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Integrative Virology Heidelberg University  69120 Heidelberg Germany"},{"name":"German Center for Infection Research  69120 Heidelberg 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