Milademetan (DS-3032) tosylate hydrate 是特异性的、具有口服活性的MDM2抑制剂,用于急性髓系白血病和实体肿瘤的研究。Milademetan (DS-3032) tosylate hydrate 可诱导 G1 细胞周期阻滞、衰老和凋亡。
生物活性 | Milademetan (DS-3032) tosylate hydrate is a specific and orally activeMDM2inhibitor for the research of acute myeloid leukemia (AML) or solid tumors. Milademetan (DS-3032) tosylate hydrate inducesG1 cell cycle arrest, senescence andapoptosis[1][2]. |
体外研究 (In Vitro) | Milademetan (DS-3032) can stabilizeTP53and selectively induce CDKNA1, BAX and MDM2 expression in neuroblastoma cells with wild-typeTP53[3]. Milademetan (DS-3032b) treatment enhancesTP53target gene expression and inducesG1 cell cycle arrest, senescence andapoptosis[3]. Milademetan (DS-3032b, 0-2000 nM) treatment selectively inhibits viability, proliferation and migration of neuroblastoma cells with wildtypeTP53independently of MYCN status[4].
Cell Viability Assay[4] Cell Line: | SK-N-SH, SH-SY5Y, IMR32, IMR5 and LAN5 cell lines. | Concentration: | 0-2000 nM. | Incubation Time: | 24-72 h. | Result: | Reduced viability in a dose- and time-dependent manner. Exhibited IC50 values of 21.9 nM, 17.7 nM, 52.63 nM, 25.7 nM and 44.1 nM in SK-N-SH, SH-SY5Y, IMR32, IMR5 and LAN5 cell lines, respectively (72 h). |
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体内研究 (In Vivo) | Milademetan (DS-3032b, 50 mg/kg, oral gavage) delays tumor growth and improves survival in mice xenografted with neuroblastoma cells with functionalTP53[4].
Animal Model: | SH-SY5Y xenograft tumors in nude mice[4]. | Dosage: | 50 mg/kg. | Administration: | Oral gavage for 30 consecutive days with an alternating schedule of 4 days of daily treatment with oral gavages followed by 2 days without treatment (4+2). | Result: | Survival in the mouse cohort was significantly prolonged. Reduced neuroblastoma xenograft tumor growth by activatingTP53signaling. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | 4°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
溶解性数据 | In Vitro: DMSO : 50 mg/mL(61.82 mM;Need ultrasonic) 配制储备液 1 mM | 1.2365 mL | 6.1825 mL | 12.3649 mL | 5 mM | 0.2473 mL | 1.2365 mL | 2.4730 mL | 10 mM | 0.1236 mL | 0.6182 mL | 1.2365 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 (sealed storage, away from moisture and light)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 5 mg/mL (6.18 mM); Suspended solution; Need ultrasonic
此方案可获得 5 mg/mL (6.18 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 5 mg/mL (6.18 mM); Suspended solution; Need ultrasonic
此方案可获得 5 mg/mL (6.18 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 5 mg/mL (6.18 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (6.18 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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