MMRi-62

通过引起细胞死亡，MMRi62 可以防止胰腺导管腺 (PDAC) 增殖、克隆和有性生长 [1]。 MMRi62 连接至 MDM2 和 MDM4 的环状异二聚体（3 nM-100 μM；4 小时）。 Albino 细胞被 MMRi62（10 nM-1 μM；72 h）激活和抑制，IC50 值为 0.34 μM (HL60) 和 0.22 μM (HL60VR)[2]。呈剂量依赖性，5μM、10μM； 24 小时）降低 MDM2B 自身泛素化并增强 MDM4 泛素化 [2]。称为 MMRi62 的 E3 连接酶修饰会导致底物偏好从 MDM2 变为 MDM4 [2]。细胞荧光由 MMRi62（5 μM；24、72 小时）传输，无需 p53 的帮助[2]。

MMRi62 在原位异种移植 PDAC 肿瘤模型中表现出抗活性，通过抑制 NCOA4 和突变 p53 转录来减少小鼠肿瘤的发展 [1]。 MMRi62 还完全阻止原位肿瘤的发展 [1]。

蛋白质印迹分析[2]
细胞类型： WT-p53 和 MV4-11 细胞；转染 MDM2B 和 MDM4 的 293 细胞
测试浓度：2、2.5、5、10、40、80、160 μM
孵育时间：24 小时（ hrs（小时））
实验结果：2 μM wt-p53 MV4-11 细胞中裂解的 PARP 蛋白和活化的 caspase 3 水平在 24 小时内增加。在 5 μM 和 10 μM 浓度下持续 24 小时，MDM2B 自身泛素化减弱，MDM4 泛素化增强。在 NALM6 细胞中，5 μM 会诱导 MDM4 蛋白的 MDM2 依赖性降解。

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细胞增殖测定[2]
细胞类型：原代 AML 患者细胞、NALM6 细胞和 NALM6shp53 细胞
测试浓度： 1、 10、25 和 50 µM
孵育时间： 24 小时和 72 小时
实验结果： 主要在 24 只手上诱导的细胞 NALM6 细胞在 AML 患者中诱导细胞凋亡 72 小时。

[1]. Li J, et al. Small-Molecule MMRi62 Induces Ferroptosis and Inhibits Metastasis in Pancreatic Cancer via Degradation of Ferritin Heavy Chain and Mutant p53. Mol Cancer Ther. 2022 Apr 1;21(4):535-545.
[2]. Lama R, et al. Small molecule MMRi62 targets MDM4 for degradation and induces leukemic cell apoptosis regardless of p53 status. Front Oncol. 2022 Aug 5;12:933446.

C21H15CL2N3O

396.27

395.0592

C, 63.65; H, 3.82; Cl, 17.89; N, 10.60; O, 4.04

352693-80-2

352693-80-2

Solid

C1=CC=NC(=C1)NC(C2=C(C(=CC=C2)Cl)Cl)C3=C(C4=C(C=CC=N4)C=C3)O

FMUBUUSODRAEMS-UHFFFAOYSA-N

InChI=1S/C21H15Cl2N3O/c22-16-7-3-6-14(18(16)23)20(26-17-8-1-2-11-24-17)15-10-9-13-5-4-12-25-19(13)21(15)27/h1-12,20,27H,(H,24,26)

7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol

MMRi 62; MMRi62; MMRi-62

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~62.5 mg/mL (~157.7 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。