MD-224 是基于蛋白水解定位嵌合体 (PROTAC) 的高效小分子 (MDM2) 降解物。MD-224 由Cereblon和MDM2配体组成。MD-224 在人白血病细胞中,诱导 MDM2 的快速降解 (<1 nm),抑制 rs4;11 细胞生长的IC50值为 1.5 nM。MD-224 有可能成为一类新的抗癌剂。
生物活性 | MD-224 is a first-in-class and highly potent small-molecule human murine double minute 2 (MDM2) degrader based on the proteolysistargeting chimera (PROTAC) concept. MD-224 consists of ligands forCereblonandMDM2. MD-224 induces rapid degradation ofMDM2at concentrations<1 nm in human leukemia cells, and achieves anIC50value of 1.5 nM in inhibition of growth of RS4;11 cells. MD-224 has the potential to be a new class of anticancer agent[1]. |
IC50& Target[1] | |
体外研究 (In Vitro) | MD-224 (1-30 nM; 2 hours) effectively induces depletion of MDM2 protein and concurrently accumulation of p53 protein in a dose-dependent manner in RS4;11 cells[1].MD-224 (30 nM; 6 hours) is more potent than MI-1061 in induction of transcriptional upregulation of these p53 target genes but have no effect on TP53 itself in RS4;11 cells[1].MD-224 (0.001-1 μM; 24 hours) induces robust apoptosis at ≤10 nM in a dose-dependent manner upon a 24 hours treatment[1].
Western Blot Analysis[1] Cell Line: | RS4;11 cells | Concentration: | 1 nM; 3 nM; 10 nM; 30 nM | Incubation Time: | 2 hours | Result: | Decreased MDM2 protein and accumulated of p53 protein. |
RT-PCR[1] Cell Line: | RS4;11 cells | Concentration: | 30 nM | Incubation Time: | 6 hours | Result: | Upregulated p53 target gene expression. |
Apoptosis Analysis[1] Cell Line: | RS4;11 cells | Concentration: | 0.001 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM | Incubation Time: | 24 hours | Result: | Induces robust apoptosis in RS4;11 cells. |
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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 | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 100 mg/mL(112.38 mM;Need ultrasonic) 配制储备液 1 mM | 1.1238 mL | 5.6192 mL | 11.2385 mL | 5 mM | 0.2248 mL | 1.1238 mL | 2.2477 mL | 10 mM | 0.1124 mL | 0.5619 mL | 1.1238 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。 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: ≥ 7.5 mg/mL (8.43 mM); Clear solution
此方案可获得 ≥ 7.5 mg/mL (8.43 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 75.0 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: 7.5 mg/mL (8.43 mM); Suspended solution; Need ultrasonic
此方案可获得 7.5 mg/mL (8.43 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 75.0 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: 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: 2.5 mg/mL (2.81 mM); Suspended solution; Need ultrasonic 4. 请依序添加每种溶剂: 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (2.81 mM); Suspended solution; Need ultrasonic *以上所有助溶剂都可在本网站选购。
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