ADH-6 是一种三吡啶酰胺化合物。ADH-6 消除了突变 p53 DBD 的聚集成核亚结构域的自组装。ADH-6 靶向并解离人类癌细胞中的突变 p53 聚集体，从而恢复 p53 的转录活性，导致细胞周期停滞和细胞凋亡 (apoptosis)。ADH-6 具有研究癌症疾病的潜力。
| 生物活性 | ADH-6 is a tripyridylamide compound. ADH-6 abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. ADH-6 targets and dissociates mutant p53 aggregates in humancancercells, which restores p53's transcriptional activity, leading to cell cycle arrest andapoptosis. ADH-6 has the potential for the research ofcancerdiseases[1]. |
体外研究
(In Vitro) | ADH-6 (25 μM, 10 h) inhibits aggregation of pR248W (indicated by dot blot assay)[1].
ADH-6 (5 μM, 6 h) dissociates intracellular mutant p53 aggregates in MIA PaCa-2 cells[1].
ADH-6 (0-10 μM, 24 or 48 h) causes selective cytotoxicity in cancer cells bearing mutant p53 (MIA PaCa-2)[1].
ADH-6 (5 μM, 24 h) 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. |
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体内研究
(In Vivo) | ADH-6 (intraperitoneal injection, 15 mg/kg, every 2 days, for a total of 12 doses) 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 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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