Restores mutant p53 activity. Binds p53 DNA binding domain (Kd
= 1-2 μ
M) and restores wild-type function to many oncogenic mutants by acting as a chaperone. Inhibits ubiquitination of p53 by HDM2. Triggers apoptosis in tumor cell lines and reduces tumor growth in a xenograft model.
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SCH529074, a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth-suppressive function to mutant p53 and interrupts HDM2-mediated ubiquitination of wild type p53.
Demma et al.
Translational approaches targeting the p53 pathway for anti-cancer therapy.
Essmann & Schulze-Osthoff