Table 1

Small molecules targeting p53–MDM2 interaction for the activation of the p53 pathway in haematological malignancies

MoleculeTargetDisease indicated
Activating wild type p53
*NutlinMDM2, p53-MDM2 interactionAML,42 43 45 ALL,56 B-CLL,46–49 MCL,52 53 HL,50 51 MM40 41
MI-63MDM2, p53-MDM2 interactionB-CLL37
RITAp53, p53-MDM2 interactionAML,61 B-CLL61
Activating mutant p53
PRIMA-1p53B-CLL,68 AML69
CP-31398p53Lymphoblastoid70
*Nutlinp53MCL,53 †ALK+ALCL71
Synergistic response of nutlin
Doxorubicinp53, MDM2AML,42 B-CLL,46 48 HL,51 MCL,53 ALK+ALCL71
Chlorambucilp53, MDM2B-CLL46 48
Fludarabinep53, MDM2B-CLL46–48
Bortezomibp53, MDM2MCL53
Melphalanp53, MDM2MM40
Etoposidep53, MDM2MM40
TRAILp53, MDM2ALK+ALCL,71 AML75
Synergistic response of other drugs
RITA + fludarabinep53, MDM2CLL61
RITA + PRIMA-1p53, MDM2AML61

  • ↵* Activate both wild type and mutant p53.

  • ↵† Activate mutated but partially functional p53.