Cellular activity upregulation of the thermolabile p53 cancer mutant Y220C by small molecule indazole derivatives.

ABSTRACT: The TP53 gene is one of the most frequently mutated genes in human cancers. Mutations often result in loss of tumor-suppressive functions and acquisition of oncogenic properties by p53, contributing to tumor progression and resistance to therapy. Among structural p53 mutations, Y220C is particularly notable for creating a surface-exposed hydrophobic pocket that destabilizes the protein while preserving partial function, making it a promising target for pharmacological reactivation. In this study, we performed a structure-guided phenotypic screen of an in-house heterocyclic compound library to identify novel small-molecule modulators of p53-Y220C. This led to the identification of a series of (1H-pyrrol-1-yl)indazole derivatives (JC16, JC36, JC65), structurally inspired by known Y220C binde

SUBMITTER: Khadiullina R 

PROVIDER: S-EPMC12594860 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature