Zinc, a promising mineral for misfolded p53 reactivation

Targeting the MDM2/MDM4 interaction interface as a promising approach for p53 reactivation therapy.

Restoration of wild-type p53 tumor suppressor function has emerged as an attractive anticancer strategy. Therapeutics targeting the two p53-negative regulators, MDM2 and MDM4, have been developed, but most agents selectively target the ability of only one of these molecules to interact with p53, leaving the other free to operate. Therefore, we developed a method that targets the activity of MDM...

p53 reactivation

Lack of p53 expression or expression of mutant p53 is common in human cancers and is associated with increased tumor growth and resistance to therapies. Significant efforts toward pharmaceutical reactivation of defective p53 by small molecules are therefore underway, targeting the different means that inactivate p53. Indeed, reactivated p53 can lead to tumor destruction. A recent paper in Cance...

Allele-specific p53 mutant reactivation.

Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the National Cancer Institute's anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53(R175) mutant. Mechanistic studies reveal that NSC319726 restores WT structure and...

Chemical Variations on the p53 Reactivation Theme

Among the tumor suppressor genes, p53 is one of the most studied. It is widely regarded as the "guardian of the genome", playing a major role in carcinogenesis. In fact, direct inactivation of the TP53 gene occurs in more than 50% of malignancies, and in tumors that retain wild-type p53 status, its function is usually inactivated by overexpression of negative regulators (e.g., MDM2 and MDMX). H...

Camphor as a promising insecticude for control