Table 2 Compounds with the ability to reactivate mutp53
From: Targeting mutant p53 for cancer therapy: direct and indirect strategies
Compound name | Mechanism | Mutant p53 target | References |
|---|---|---|---|
CP-31398 | CP-31398 binds to the denatured DNA-binding domain of mutp53 and restores nature p53 conformation | V173A, S241F, R249S, R273H | [155] |
PRIMA-1 | PRIMA-1 enhances wtp53 stability at 37 °C, induces a conformational change of mutp53 and restores their DNA binding ability | R175H, R273H | [156] |
APR-246 | APR-246 enhances wtp53 stability at 37 °C, induces a conformational change of mutp53 and restores their DNA binding ability | R175H, R273H | [156] |
MIRA-1 | MIRA-1 prevents unfolding of wtp53 and mutp53 and restores native wtp53 conformation | R175H, R248Q, R273H | [157] |
STIMA-1 | STIMA-1 binds to the core domain of mutant p53 and results in the stabilization of wtp53 conformation | R175H, R273H | [158] |
PK11000 | PK11000 increases the Tm of mutp53 to promote correct fold | Y220C | [159] |
ZMC1 | ZMC1 provides addition Zn2+ to cancer with mutp53 for proper folding | R175H, R172H | [160] |
COTI-2 | COTI-2 converts mutp53 to wild-type form | R175H | [161] |
pCAPs | pCAPs binds to the core domain of mutp53 | I195T | [47] |
Reacp53 | Reacp53 prevents mutp53 amyloid aggregation | P53 252–258 amyloid zipper structure | [162] |
RETRA | RETRA releases p73 from mutp53-p73 complex | P73 | [163] |
PK083 | PK083 binds and stabilizes p53-Y220C to restore its transcriptional activity | Y220C | [164] |
P53R3 | P53R3 restores sequence-specific DNA-binding ability of several mutp53 | R175H, M237I, R273H | [165] |
SCH529074 | SCH529074 enables mutp53 to bind to a consensus p53 DNA-binding site | R175H, L194F, R248W, R249S, R273H | [166] |
PK7088 | PK7088 selectively binds to the specific surface cavity of p53 Y220C to destabilize it and restores wtp53 conformation | Y220C | [167] |
Stictic acid | Stictic acid blocks the pocket between loop L1 and sheet S3 of p53 core domain and reactivates mutp53 | R175H, G245S | [168] |
Chetomin | Chetomin promotes Hsp40 expression and the p53-Hsp40 binding to restore wtp53 conformation | R175H | [169] |
RITA | RITA restores transcriptional activity of mutp53 | I254D, R175H, R213Q, Y234H, R248W/Q, R273H, R280K | [170] |
WR1065 | WR1065 restores temperature-sensitive mutp53 native conformation | V272M | [171] |
Adamantyl isothiocyanates | Adamantyl isothiocyanates rescues mutp53 R206K and R273H and results in the upregulation of canonical wtp53 targets and ATM phosphorylation | R280K, R273H | [172] |