Table 3 Compounds directly target mutp53
From: Targeting mutant p53 for cancer therapy: direct and indirect strategies
Compound name | Mechanism | Targets | References |
|---|---|---|---|
Hsp90 inhibitor | Hsp90 inhibitor prevents Hsp90 chaperone from binding to mutp53 and promotes mutp53 proteins degradation | R175H, L194F, R248Q, R273H, R280K, R172H (mouse) | [173] |
HDAC inhibitor | HDAC inhibitor inhibits HDAC-regulated transcription and disrupts HDAC6/Hsp90/mutp53 complex | R175H, R280K, V247F/P223L | [56] |
Statins | Statins inhibits the interaction between mutp53 and DNAJA1 to induce CHIP-dependent p53 degradation | V157F, R172H, R175H, Y220C, R248W, R273H, R280K | [174] |
Gambogic acid | Gambogic acid increases wtp53 proteins levels, inhibits mutp53-Hsp90 complex and induces CHIP-mediated degradation | R175H, G266E, R273H, R280K | [58] |
Spautin-1 | Spautin-1 inhibits macroautophagy to induce mutp53 degradation via chaperone-mediated autophagy | P98S, P151H, A161T, R175C, R175D, R175H, L194F, S227K, S227R, G245C, R248L, R248W, E258K, R273H, R273L, R280K, and R282W | [99] |
NSC59984 | NSC59984 promotes MDM-mediated mutp53 protein degradation and stimulating p73 | R175L, R175H, S241F, R273H/P309F | [175] |
Disulfiram (DSF) | Disulfiram catalyzes both wtp53 and mutp53 through the 26S proteasome pathway | R273H | [176] |