Development of a chemical probe against NUDT15

• Published in: Nature chemical biology Vol. 16; no. 10; pp. 1120 - 1128
• Main Authors: Zhang, Si Min, Desroses, Matthieu, Hagenkort, Anna, Valerie, Nicholas C. K., Rehling, Daniel, Carter, Megan, Wallner, Olov, Koolmeister, Tobias, Throup, Adam, Jemth, Ann-Sofie, Almlöf, Ingrid, Loseva, Olga, Lundbäck, Thomas, Axelsson, Hanna, Regmi, Shruti, Sarno, Antonio, Krämer, Andreas, Pudelko, Linda, Bräutigam, Lars, Rasti, Azita, Göttmann, Mona, Wiita, Elisée, Kutzner, Juliane, Schaller, Torsten, Kalderén, Christina, Cázares-Körner, Armando, Page, Brent D. G., Krimpenfort, Rosa, Eshtad, Saeed, Altun, Mikael, Rudd, Sean G., Knapp, Stefan, Scobie, Martin, Homan, Evert J., Berglund, Ulrika Warpman, Stenmark, Pål, Helleday, Thomas
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2020; Nature Publishing Group
• Subjects: 631/337/1644; 631/67; 631/92/556; 631/92/613; Binding Sites; Biochemical Engineering; Biochemistry; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biologi; Biological Sciences; Biology; Bioorganic Chemistry; Biophysics; Cell Biology; Cell Line; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Drug Design; Drug Development; Enzymes; Escherichia coli; Health services; Humans; Hydrolase; Inflammatory diseases; Inorganic Pyrophosphatase - antagonists & inhibitors; Inorganic Pyrophosphatase - genetics; Inorganic Pyrophosphatase - metabolism; Laboratories; Lead compounds; Leukemia; Medical research; Medicin och hälsovetenskap; Metabolism; Metabolites; Models, Molecular; Natural Sciences; Naturvetenskap; Nucleic acids; Nucleotides; Physiology; Protein Binding; Protein Conformation; Pyrophosphatases - antagonists & inhibitors; Pyrophosphatases - chemistry; Pyrophosphatases - genetics; Pyrophosphatases - metabolism; Structure-Activity Relationship; Thioguanine; Toxicity

The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless,...