p53 activator APR-246

A quinuclidinone derivative that targets the Wrap53 gene with potential antineoplastic activity. p53 activator APR-246 binds to and activates transcription of the Wrap53 gene, which results in an increase in WRAP53 p53 antisense transcript levels and, potentially, an increase in native p53 activity; in turn, increased p53 activity may lead to an induction of cell cycle arrest and apoptosis in tumor cells. This agent may work synergistically with other antineoplastic agents. p53, a tumor suppressor and transcription factor normally activated upon DNA damage, is mutated or absent in various cancer cell types and plays a key role in DNA repair and the induction of apoptosis. The Wrap53 transcript, a natural p53 antisense transcript, regulates endogenous p53 mRNA levels and additional induction of p53 protein by targeting the 5′ untranslated region of p53 mRNA.