Table 1 Some major approaches towards p53 reactivation and tumor regression
Synthesized drugs/small molecules | |||
|---|---|---|---|
Drug | Status of p53 | Study conclusion | Refs |
PRIMA-1 | amyloid aggregation of mutant p53 | Restore unfolded p53 mutants to a native that can induces apoptosis and activates several p53 target genes | [109] |
MIRA-1 | Mutant p53 | Inhibits viability, colony formation, and migration. Apoptosis of Multiple Myeloma cells irrespective of p53 status sue to upregulation of Puma and Bax along with downregulation of Mcl-1 and c-Myc | [152] |
RETRA | Mutant p53 | Activates several p53-regulated genes and specifically suppresses mutant p53-bearing tumor cells in vitro and in mouse xenografts |  |
MB710, aminobenzothiazole derivative | oncogenic p53 mutation Y220C | Binds tightly to the pocket of Y220C mutant and stabilizes p53-Y220C in vitro | [153] |
MB725, an ethylamide analogue of MB710 | oncogenic p53 mutation Y220C | Increased expression of p53 target genes such as BTG2, p21, PUMA, FAS, TNF, and TNFRSF10B, promoting apoptosis and cell cycle arrest | [153] |
PK11007 (2-Sulfonylpyrimidines) | Mutant p53 | Unstable p53 reactivation in some cancer cell lines, resulting in upregulation of p53 target genes, p21 and PUMA | [154] |
Pramlintide | Null p53 | Rapid tumour regression in p53-deficient thymic lymphomas | [155] |
PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine | Mutant p53 | Can binds to a mutant form increasing the melting temperature of the protein to slow down its rate of aggregation | [156] |
17-AAG- Inhibitor of HSP90 | Mutant p53 | Stimulate the heat shock transcription factor (HSF-1) and upregulate the endogenous HSP70 that results in the formation of soluble folding intermediates of cytoplasmic p53 R175H | [157] |
Natural products | |||
 Propolis, resinous substance produced by honeybees | Wildtype/mutant | Activation of p53-GADD45 signaling resulting in growth arrest of cancer cells | [158] |
 Curcumin-based Zn(II)-complex | Mutant p53 | Restoring transactivation functions and inducing apoptotic cell death | [159] |
Genetic modulation | |||
 Deletion of ΔNp63 and ΔNp73 | Null p53 | Upregulation of key metabolic regulators such as IAPP, GLS2, and TIGAR thereby increasing apoptosis and tumor regression | [160] |