Table 1.

Published strategies and compounds tested for mutp53 aggregation inhibition.

Structure/Compound	Mut/WT Aggregates	Model	Outcomes	Refs
Therapeutic strategy: thiol alkylating agents targeting mutp53 cysteines
PK11000	Y220C	in vitro	- Prevents aggregation of Y220C mutp53c.	[60]
PRIMA-1	Wild-type, R248Q and R280K	in vitro	- Prevents aggregation of wtp53c and R248Q. - Inhibits seeding promoted by R280K in cell lysates. - Disrupts mutp53 aggregation in cells. - Induces apoptosis.	[33]
Therapeutic strategy: designed peptides for complementary binding to regions of p53 with a greater propensity to aggregate.
ReACp53	R248Q, P223L, V274F, R233H, Q331R, and H1299 cells transfected with R282W and R248W	in vitro and in vivo	- Prevents aggregation of the peptide LTIITLE (p53 residues 252–258). - Less PAb 240 staining; - Shows significant SDS resistance. - Significantly increases p21, GADD45B, PUMA, NOXA and DRAM1 mRNA. - Causes tumor regression and reduction of Ki67-positive cells. - Association with carboplatin shows increased mouse survival and induction of apoptosis.	[25,61,62,63]
Therapeutic strategy: compounds with metallochaperone- or molecular chaperone-based mechanisms
LI	Y220C	in vitro	- Prevents aggregation of Y220C mutp53c. - Reduces the colocalization of p53 and amyloid oligomers. - Increases the Zn2+ influx, indicating Zn-metallochaperone activity	[64]
PK9318	Y220C	in vitro	- Prevents aggregation of Y220C mutp53c; - Reduces cell viability.	[65]
Therapeutic strategy: miscellaneous compounds with anti-protein aggregation properties previously tested in neurodegenerative diseases.
Acetylcholine Chloride	R248W	in vitro	- Prevents aggregation of the peptide WRPILTIITL bearing the R248W mutant.	[66]
Resveratrol	wtp53 and R248Q	in vitro and in vivo	- Prevents aggregation of wtp53c and R248Q mutp53c. - Disrupts mutp53 aggregation in cells. - Prevents cell migration and proliferation.	[67]
ADH-6	R248W	in vitro and in vivo	- Prevents aggregation of the mutant mimetic peptide R248W (WRPILTIITLEDSSGNLLGRNSFEVR). - Disrupts and reactivates mutp53 aggregates. - Induces apoptosis and changes cell cycle with more cells in the G0/G1 phase. - Shows tumor regression and less PAb 240 staining of tumor tissue.	[61]
Polyarginine (A) and polyornithine (B)	R248Q	in vitro	- Prevents aggregation of the peptide QRPILTIITL bearing the R248Q mutant. - Inhibits proliferation in cells. - Has no toxicity to normal cells. Polyornithine increases p21 levels in cells.	[68]