Article
A Tale of Two Mechanisms: The p53 Modulator COTI-2 Is a Zn Metallochaperone.
Drug development research - 1 Aug 2026
Şimşek İrem, Shahbazi-Raz Farsheed, Krause Michael J, Mohammadzadeh Azam, Kosar Maryam, Xu Peihan, Khan Samra, Tykhoniuk Olena, DaDalt Ashley, Almasri Deya'a, Watanabe Lara K, Breault Kaitlyn, Hayward John J, Pick Fraser S, Ho Richard L, Rawson Jeremy M, Trant John F
Abstract excerpt
Mutations in, or misregulation of, Tp53 are found in approximately 50% of all cancers. p53 functions by ensuring that cells with irretrievably damaged DNA undergo apoptosis. Tp53 mutations often induce conformational changes that inhibit activity; however, small-molecule chaperones could theoretically restore conformation and activity. COTI-2, a thiosemicarbazone with orphan-drug status for ovarian cancer, has...
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