Figure 1.

Proposed mechanism of action of APR-246 in TP53-mutated acute lymphoblastic leukemia. Acute lymphoblastic leukemia (ALL) cells expressing mutant p53 are refractory to doxorubicin-induced apoptosis. APR-246 is taken up by cells and metabolized into the reactive electrophile methylene quinuclidinone (MQ). By refolding p53 into an active conformation, MQ restores the apoptosis-inducing effects of doxorubicin. In addition, an increase in oxidative stress brought about by MQ may further enhance apoptosis induction.