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. 2022 Oct 13;12:1023427. doi: 10.3389/fonc.2022.1023427

Table 1.

Agents that target TP53 mutation.

Compound Mechanism References
PRIMA-1 restore the wild-type conformation to mutant P53 and induce apoptosis in cancer cells (128)
APR-246(PRIMA-1Met) restore the wild-type conformation to mutant P53 and induce apoptosis in cancer cells (129, 130)
reduce glutathione(GSH) and thioredoxin reductase 1 (TXNRD1)
increase ROS levels
COTI-2 promote refolding of mutant p53 and restore wild-type-p53 function (124, 131)
lead to activation of AMPK and inhibit the PI3K-AKT pathway
MIRA1 restore transcriptional transactivation to mutant p53 in living cells (132)
STIMA-1 preferentially kill mutant p53‐carrying tumor cells  (133)
activate caspases and induces Bax, PUMA and p21
Zinc metallochaperone-1 (ZMC1/NSC319726) activate mutant p53 by restoring proper zinc loading (134, 135)
decrease cellular GSH levels and increase ROS levels
PK11007 and other similar compounds(PK11000,PK11010,PK11029,PK11003,PK11012 and PK11015) alkylation of surface-exposed cysteines 182 and 277 and stabilized the p53 DBD without impairing its DNA-binding affinity (126)
increase protein and mRNA levels of the p21 and PUMA
decrease cellular GSH levels and increase ROS levels
ReACp53 and related peptides(CDB3) disrupts mutant-p53 aggregates and stabilise wild-type conformation (136138)
CP-31398 protect p53 from thermal degeneration,restore the wild type function of some mutant p53 and up-regulate p53 levels (139, 140)
PhiKan083(PK083) Binds to the DNA-binding domain of mutant-p53 and restore the wild type function of some mutant p53 (141143)
RETRA Treatment of mutant p53-expressing cancer cells with RETRA results in a substantial increase in the expression level of p73 (144)
PC14586 stabilize the Y220C mutant and restore p53 wild-type (normal) conformation (145)
MDM2 Inhibitor:Nutlin-3 and ALRN-6924 Increase p53 levels and activity (146, 147)
RG7388 and AMG232 disrupt the p53-MDM2 protein–protein interaction and prevent p53 from proteasomal degradation (148, 149)