ADH-6 TFA 是一种三吡啶酰胺化合物。ADH-6 TFA 消除了突变 p53 DBD 的聚集成核亚结构域的自组装。ADH-6 TFA 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 TFA 具有研究癌症疾病的潜力。
| 生物活性 | 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 humancancercells, which restores p53's transcriptional activity, leading to cell cycle arrest andapoptosis. ADH-6 TFA has the potential for the research ofcancerdiseases[1]. |
体外研究
(In Vitro) | 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. |
|
体内研究
(In Vivo) | 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 |
|
| 分子量 | |
| 性状 | |
| Formula | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(132.51 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.3251 mL | 6.6254 mL | 13.2508 mL | | 5 mM | 0.2650 mL | 1.3251 mL | 2.6502 mL | | 10 mM | 0.1325 mL | 0.6625 mL | 1.3251 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
m.cnreagent.com