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]