ADH-6 TFA is a tripyridylamide compound. ADH-6 abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. ADH-6 TFA targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53's transcriptional activity, leading to cell cycle arrest and apoptosis. ADH-6 TFA has the potential for the research of cancer diseases[1].
ADH-6 (25 μM, 10 h) TFA inhibits aggregation of pR248W (indicated by dot blot assay)[1].
ADH-6 (5 μM, 6 h) TFA dissociates intracellular mutant p53 aggregates in MIA PaCa-2 cells[1].
ADH-6 (0-10 μM, 24 or 48 h) TFA causes selective cytotoxicity in cancer cells bearing mutant p53 (MIA PaCa-2)[1].
ADH-6 (5 μM, 24 h) TFA specifically targets and reactivates aggregation-prone mutant p53 in MIA PaCa-2 cells[1].
Cell Viability Assay[1]
| Cell Line: | MIA PaCa-2 (mutant R248W p53), SK-BR-3 (mutant R175H p53) |
| Concentration: | 0, 2.5, 5, 7.5, 10 μM |
| Incubation Time: | 24, 48 h |
| Result: | Caused death of cancer cells bearing mutant, but not WT, p53. |
Western Blot Analysis[1]
| Cell Line: | MIA PaCa-2 cells |
| Concentration: | 5 μM |
| Incubation Time: | 24 h |
| Result: | Increased expression of p53-inducible MDM2 and proapoptotic Bax. |
ADH-6 (intraperitoneal injection, 15 mg/kg, every 2 days, for a total of 12 doses) TFA causes regression of mutant p53-bearing tumors [1].
| Animal Model: | MIA PaCa-2 xenografts[1] |
| Dosage: | 716.4 µM in 0.02% DMSO |
| Administration: | Intraperitoneal injection, every 2 days, for a total of 12 doses |
| Result: | Reduced tumor growth relative to the saline-treated control group. Reduced mutant p53 levels and shrinked xenografts harboring aggregation-prone mutant p53. |
| Animal Model: | MIA PaCa-2 xenografts (pharmacokinetics assay)[1] |
| Dosage: | 15 mg/kg |
| Administration: | Intraperitoneal injection, for a single dose |
| Result: | Cmax: 21 µg/mL, T1/2: 3.6 h |