MD-224 是一种作用强大的MDM2蛋白降解剂，由Cereblon和MDM2配体组成，能够促使MDM2蛋白迅速降解。
Cas No.:2136247-12-4
Sample solution is provided at 25 µL, 10mM.
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MD-224, a highly potent PROTAC degrader of MDM2 that is composed of Cereblon and MDM2 ligand, induces rapid degradation of the MDM2 protein [1]. MD-224 binds to the pregnane X receptor (PXR) outside the ligand-binding pocket at a structural motif and can induce the degradation of multiple nuclear receptors[2]. MD-224 has been widely used to inhibit the growth of tumor cells in a p53-independent manner and induce tumor regression in mouse xenograft models[3].
In vitro, MD-224 treatment for 4 days significantly inhibited the proliferation of RS4;11 cells, with an IC50 value of 1.5nM[4].
In vivo, MD-224 treatment via intravenous injection at a dose of 50mg/kg, once every other day for 3 weeks, significantly inhibited tumor growth in the RS4;11 xenograft mouse model without causing weight loss in the mice[4].
References:
[1] Yang J, Li Y, Aguilar A, et al. Simple structural modifications converting a bona fide MDM2 PROTAC degrader into a molecular glue molecule: a cautionary tale in the design of PROTAC degraders[J]. Journal of medicinal chemistry, 2019, 62(21): 9471-9487.
[2] Huber A D, Lin W, Jung Y H, et al. PROTAC repurposing uncovers a noncanonical binding surface that mediates chemical degradation of nuclear receptors[J]. Nature Communications, 2025, 16(1): 9805.
[3] Han X, Wei W, Sun Y. PROTAC degraders with ligands recruiting MDM2 E3 ubiquitin ligase: an updated perspective[J]. Acta materia medica, 2022, 1(2): 244.
[4] Li Y, Yang J, Aguilar A, et al. Discovery of MD-224 as a first-in-class, highly potent, and efficacious proteolysis targeting chimera murine double minute 2 degrader capable of achieving complete and durable tumor regression[J]. Journal of medicinal chemistry, 2018, 62(2): 448-466.
MD-224 是一种作用强大的MDM2蛋白降解剂，由Cereblon和MDM2配体组成，能够促使MDM2蛋白迅速降解[1]。MD-224能够以特定的结构基序结合pregnane X receptor (PXR)（位于配体结合口袋之外），并可诱导多种核受体的降解[2]。MD-224已被广泛用于以不依赖p53的方式抑制肿瘤细胞生长，并在小鼠异种移植模型中诱导肿瘤消退[3]。
在体外，MD-224处理RS4;11细胞4天，显著抑制了细胞增殖，IC50值为1.5nM[5]。
在体内，MD-224通过静脉注射给药，剂量为50mg/kg，每隔一天一次，持续3周，显著抑制了RS4;11异种移植小鼠模型中的肿瘤生长，且未导致小鼠体重减轻[4]。
| Cell experiment [1]: | |
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Cell lines |
RS4;11 cells |
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Preparation Method |
RS4;11 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and antibiotics (penicillin 100U/ml, streptomycin 0.1mg/ml) under normal conditions (5% CO2 with 95% humidified air). RS4;11 cells (1×104 per ml) were seeded in 96-well cell culture plates in 100μl of culture medium. After addition of the different concentrations of MD-224 (0.1, 1, 10, and 100nM), the cells were incubated for 4 days at 37°C in an atmosphere of 5% CO2. Cell growth was evaluated. |
|
Reaction Conditions |
0.1, 1, 10, and 100nM; 4 days |
|
Applications |
MD-224 treatment reduced the cell viability of RS4;11 cells in a dose-dependent manner. |
| Animal experiment [1]: | |
|
Animal models |
SCID mice |
|
Preparation Method |
SCID mice (eight-week-old) were housed in a temperature/humidity-controlled room on a 12h/12h light/dark cycle with free access to food and water. 5×106 RS4;11 cells with 50% Matrigel were injected subcutaneously on the dorsal side of SCID mice. When tumors reached 100mm3, mice were randomly assigned to treatment and vehicle control groups. MD-224 treatment (i.v.) at 50mg/kg, every other day for three weeks. Tumor size was measured 2-3 times per week by electronic calipers during the treatment period and at least weekly after the treatment was ended. |
|
Dosage form |
50mg/kg; every other day for three weeks; i.v. |
|
Applications |
MD-224 treatment significantly reduced tumor growth in the RS4;11 xenograft mouse model. |
|
References: |
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| Cas No. | 2136247-12-4 | SDF | |
| Canonical SMILES | FC1=C(Cl)C=CC=C1[C@@H]2[C@@]3(C(C=CC(Cl)=C4)=C4NC3=O)C5(CCCCC5)N[C@H]2C(NC6=CC=C(C(NCCCC#CC7=C(CN(C8C(NC(CC8)=O)=O)C9=O)C9=CC=C7)=O)C=C6)=O | ||
| 分子式 | C48H43Cl2FN6O6 | 分子量 | 889.8 |
| 溶解度 | DMSO: 150 mg/mL (168.58 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1238 mL | 5.6192 mL | 11.2385 mL |
| 5 mM | 224.8 μL | 1.1238 mL | 2.2477 mL |
| 10 mM | 112.4 μL | 561.9 μL | 1.1238 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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