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Four of the seven analogs investigated had IC<jats:sub>50<\/jats:sub> values below 5\u2005\u03bcM, with the most potent compound (IA1\u20108H2) exhibiting an IC<jats:sub>50<\/jats:sub> value of 3.4\u00b10.7\u2005\u03bcM. Interestingly, these compounds appear to be non\u2010covalent, non\u2010competitive inhibitors of PHPT1 activity, in contrast to other recently reported PHPT1 inhibitors. Mutating the three cysteine residues to alanine has no effect on inhibition, indicating that cysteine is not critical for interactions between inhibitor and enzyme.<\/jats:p>","DOI":"10.1002\/cmdc.202300187","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T13:39:29Z","timestamp":1685713169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Derivatives of the Fungal Natural Product Illudalic Acid Inhibit the Activity of Protein Histidine Phosphatase PHPT1"],"prefix":"10.1002","volume":"18","author":[{"given":"Hanfei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry University of Utah College of Pharmacy  Salt Lake City UT 84112 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Robert","family":"Gaston","sequence":"additional","affiliation":[{"name":"Department of Chemistry West Virginia University  Morgantown WV 26506 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kh Tanvir","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chemistry West Virginia University  Morgantown WV 26506 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory B.","family":"Dudley","sequence":"additional","affiliation":[{"name":"Department of Chemistry West Virginia University  Morgantown WV 26506 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-9261","authenticated-orcid":false,"given":"Amy M.","family":"Barrios","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry University of Utah College of Pharmacy  Salt Lake City UT 84112 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