Table 1.
Compounds and small molecules that target wild-type and mutant p53
Molecule/compound | Mechanism of action | Target | Stage of development |
---|---|---|---|
Activate wild-type p53 | |||
Nutlins RG7112 (RO5045337) | Inhibits p53-MDM2 binding | MDM2 | Phase I clinical trial (NCT01164033, NCT01143740, NCT00623870 and NCT00559533) [48] |
Benzodiazepinediones (TDP665759) | Inhibits p53-MDM2 binding | MDM2 | Preclinical [50] |
Spiro-oxindoles (MI-219) | Inhibits p53-MDM2 binding | MDM2 | Preclinical [13] |
RITA | Inhibits p53 binding | p53 (WT and mut) | Preclinical [53] |
JNJ-26854165 (Serdemetan) | Inhibits p53-MDM2 binding | MDM2 | Phase I clinical trial (NCT00676910) [58, 60] |
Tenovin 1 and 6 | Inhibits SirT1 and SirT2 (protein deacetylators) | SirT1 and SirT2 | Preclinical [117] |
SJ-172550 | Inhibits p53:MDM2/X binding | MDMX | Preclinial [69] |
RO-2443/RO-5693 | Inhibits p53:MDM2/X binding | MDMX | Preclinical [70] |
XI-011 | Repression of MDMX promoter | MDMX | Preclinical [71] |
Re-activate mutant p53 | |||
CP-31398 | Interacts with DNA, reactive oxygen species | V173A, R175S, R249S, R273H | Preclinical [83] |
PRIMA-1 (APR-246) | Covalently modifies cysteine residues, protein folding | R273H, R175H | Phase I clinical trial (NCT00900614) [87] |
MIRA-1 | Alkylation Cysteine and lysine residues | R175H, R248 W, R248Q, R273H, R282W | Preclinical [88] |
PhiKan083 | Slows thermal denaturation | Y220C | Preclinical [25] |
NSC319726 | Zinc chelation/Redox modulation | R175H | Preclinical [32] |