| 生物活性 | Navtemadlin (AMG 232) is a potent, selective and orally available inhibitor ofp53-MDM2interaction, with anIC50of 0.6 nM. Navtemadlin binds toMDM2with aKdof 0.045 nM[1][2]. |
| IC50& Target | IC50: 0.6 nM (p53-MDM2 interaction)[1]
Kd: 0.045 nM (MDM2)[1] |
体外研究
(In Vitro) | Navtemadlin (AMG 232) (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines[1].
Navtemadlin potently inhibits proliferation of non-MDM2-amplified HCT116 colorectal cells (IC50=10 nM)[3].
Cell Viability Assay[1] | Cell Line: | SJSA-1, HCT116, ACHN, NCI-H460, MOLM-13, RKO, MCF7, 22RV1, HT-29, PC-3, NCI-H82, NCI-SNU1, MG-63, NCI-H2452, SW982, C32, SK-HEP-1, A375, RT4, RPMI2650, MDA-MB-134-VI, NCI-H2347 and A427 cells. | | Concentration: | 0-10 μM. | | Incubation Time: | 72 hours. | | Result: | Induced p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN).
Caused robust p21 mRNA induction between 9.76 and 34.9 fold with IC50 values ranging from 12.8 to 46.8 nM. |
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体内研究
(In Vivo) | Navtemadlin (AMG 232) (10, 25, 75 mg/kg, once daily, p.o.) activates p53 pathway activity in vivo[1].
Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) potently inhibits growth of tumor xenografts in mice[1].
Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) blocks DNA synthesis and induces apoptosis in vivo[1].
Navtemadlin causes a dose-dependent tumor growth inhibition with an ED50of 16 mg/kg[2].
| Animal Model: | Female athymic nude mice (n=10/group) based cancer models[1]. | | Dosage: | 10, 25, 75 mg/kg. | | Administration: | Once daily by oral gavage. | | Result: | Resulted in significant tumor growth inhibition across all models. SJSA-1, an MDM2 amplified osteosarcoma model, was the most sensitive to AMG 232 treatment with an ED50of 9.1 mg/kg. In the highest dose group of 75 mg/kg, 10/10 tumors completely regressed and were undetectable after 10 days of treatment. |
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| 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 |
*该产品在溶液状态不稳定，建议您现用现配，即刻使用。 |
| 溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(87.94 mM) H2O : ≥ 0.1 mg/mL(0.18 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.7589 mL | 8.7943 mL | 17.5886 mL | | 5 mM | 0.3518 mL | 1.7589 mL | 3.5177 mL | | 10 mM | 0.1759 mL | 0.8794 mL | 1.7589 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；该产品在溶液状态不稳定，建议您现用现配，即刻使用。 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： 50%PEG300 50% saline Solubility: 10 mg/mL (17.59 mM); Suspended solution; Need ultrasonic 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (4.40 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.40 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (4.40 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.40 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 4. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 2.5 mg/mL (4.40 mM); Clear solution 5. 请依序添加每种溶剂： PBS Solubility: 1.5 mg/mL (2.64 mM); Clear solution; Need ultrasonic *以上所有助溶剂都可在本网站选购。
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