UCI-1014 is a mutant p53 ( p53 R175H ) corrector/reactivator. UCI-1014 restores the wild-type-like DNA-binding activity of p53 R175H, promotes the redistribution of the mutant protein to chromatin, and induces the expression of p53-dependent target genes. UCI-1014 inhibits the proliferation of p53 R175H -mutant cancer cells through an SLC7A11-independent mechanism. UCI-1014 can be used for research related to p53-mutant cancers [1].
In Vitro, UCI-1014 (72 h) inhibits the proliferation of TOV-112D cells carrying p53R175H with an IC50 of 4.5 μM[1]. UCI-1014 (10-30 μM; 3 h) restores the DNA-binding ability of p53R175H in TOV-112D cells, and evidence shows that this mutant protein redistributes to the chromatin fraction after treatment with 10 μM or 30 μM for 3 hours[1]. UCI-1014 (3 h) induces p53-dependent gene expression in TOV-112D cells, with a transcriptome profile highly similar to that of UCI-1001, and it induces a greater number of p53-dependent genes after 3 hours of treatment[1]. UCI-1014 (5-20 μM; 72 h) exhibits growth inhibitory activity against TOV-112D cells, and this activity can only be partially reversed by 5 mM N-acetylcysteine, indicating that its mechanism of action differs from that of thiol-reactive compounds such as APR-246 [1].
References:
[1]. Fallatah, M. et al. (2024). Pyrimidine Triones as Potential Activators of p53 Mutants. Biomolecules, 14(8), 967
In Vitro, UCI-1014 (72 h) inhibits the proliferation of TOV-112D cells carrying p53R175H with an IC50 of 4.5 μM[1]. UCI-1014 (10-30 μM; 3 h) restores the DNA-binding ability of p53R175H in TOV-112D cells, and evidence shows that this mutant protein redistributes to the chromatin fraction after treatment with 10 μM or 30 μM for 3 hours[1]. UCI-1014 (3 h) induces p53-dependent gene expression in TOV-112D cells, with a transcriptome profile highly similar to that of UCI-1001, and it induces a greater number of p53-dependent genes after 3 hours of treatment[1]. UCI-1014 (5-20 μM; 72 h) exhibits growth inhibitory activity against TOV-112D cells, and this activity can only be partially reversed by 5 mM N-acetylcysteine, indicating that its mechanism of action differs from that of thiol-reactive compounds such as APR-246 [1].
References:
[1]. Fallatah, M. et al. (2024). Pyrimidine Triones as Potential Activators of p53 Mutants. Biomolecules, 14(8), 967