MI-773
(Synonyms: (2'R,3S,4'S,5'R)-6-氯-4'-(3-氯-2-氟苯基)-2'-(2,2-二甲基丙基)-1,2-二氢-N-(反式-4-羟基环己基)-2-氧代螺[3H-吲哚-3,3'-吡咯烷]-5'-甲酰胺) 目录号 : GC16296
MI-773 是一种有效的 MDM2-p53 蛋白-蛋白相互作用 (PPI) 抑制剂，对 MDM2 具有高结合亲和力 (Kd=8.2 nM)。 MI-773 具有抗肿瘤活性。
Cas No.:1303607-07-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Sulforhodamine B or the WST-1 cytotoxicity assay are performed to determine the effect of MI-773 on ACC cell viability. Briefly, 1 to 3×103 UM-HACC cells are plated per well, and treated with 0 to 40 μM MI-773 for 24 to 96 hours. To assess apoptosis, 2×105 cells are plated in 60 mm3 dishes, attached overnight, and treated with 0 to 20 μM MI-773 for 72 hours. Cells are lysed with a hypotonic buffer and stained with propidium iodide. Primary low passage ACC cells (UM-HACC-5) are stably transduced with lentiviral vectors expressing shRNA-p53 or scrambled sequence control shRNA-C and selected with 1.0 μg/mL puromycin[1]. |
Animal experiment: | Mice[1] To establish a patient-derived xenograft (PDX) model of ACC, human tumor fragments from the UM-HACC-5 patient are transplanted subcutaneously into the dorsal region of male severe combined immunodeficient (SCID) mice (CB.17.SCID). Two of six initial patient tumor fragments transplant, grow, and are retransplanted in vivo into new male or female mice for up to 12 passages. When tumors reach an average of 250 mm3, mice are randomized into groups and received either vehicle (polyethylene glycol-200 + D-α-tocopherol polyethylene glycol 1000 succinate), or treatment with 10, 50, or 100 mg/kg MI-773 daily by oral gavage. The ACCx6 and ACCx9 models are treated with vehicle or 100 mg/kg MI-773. |
References: [1]. Warner KA, et al. Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma. Clin Cancer Res. 2016 Jul 15;22(14):3550-9. | |
MI-773 is a small molecule inhibitor of MDM2 with IC50 value of 62nM [1].
MI-773 is a small molecule MDM2 antagonist. It is a spirooxindole derivative. MI-773 shows a high MDM2 affinity with IC50 value of 62nM in the FP competitive binding experiment. In the in vitro cell-based assay, MI-773 shows a similar inhibition efficacy with its enantiomer MI-77301. The GI50 values are 58nM and 33nM for MI-773 and MI-77301, respectively. Both MI-773 and MI-77301 exert considerable activity at dose of 100 mg/kg in mouse xenograft models of osteosarcoma, prostate cancer, colorectal cancer, leukemia or melanoma. Currently, an international and multicenter phase I trial of MI-773 is underway for patients with liposarcomas and other p53-wild-type tumors [1, 2].
References:
[1] Zak K, Pecak A, Rys B, Wladyka B, Dömling A, Weber L, Holak TA, Dubin G. Mdm2 and MdmX inhibitors for the treatment of cancer: a patent review (2011-present). Expert Opin Ther Pat. 2013 Apr;23(4):425-48.
[2] Shoushtari AN, Van Tine BA, Schwartz GK. Novel treatment targets in sarcoma: more than just the GIST. Am Soc Clin Oncol Educ Book. 2014:e488-95.
| Cas No. | 1303607-07-9 | SDF | |
| 别名 | (2'R,3S,4'S,5'R)-6-氯-4'-(3-氯-2-氟苯基)-2'-(2,2-二甲基丙基)-1,2-二氢-N-(反式-4-羟基环己基)-2-氧代螺[3H-吲哚-3,3'-吡咯烷]-5'-甲酰胺 | ||
| 化学名 | (2'R,3S,4'S,5'R,Z)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2-hydroxy-N-((1r,4R)-4-hydroxycyclohexyl)-2'-neopentylspiro[indole-3,3'-pyrrolidine]-5'-carbimidic acid | ||
| Canonical SMILES | CC(C)(C[C@](N1)([H])[C@@]([C@@]([C@]1([H])/C(O)=N/[C@]2([H])CC[C@](O)([H])CC2)([H])C3=C(F)C(Cl)=CC=C3)(C(O)=N4)C5=C4C=C(Cl)C=C5)C | ||
| 分子式 | C29H34Cl2FN3O3 | 分子量 | 562.5 |
| 溶解度 | Soluble in DMSO | 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 | 1.7778 mL | 8.8889 mL | 17.7778 mL |
| 5 mM | 0.3556 mL | 1.7778 mL | 3.5556 mL |
| 10 mM | 0.1778 mL | 0.8889 mL | 1.7778 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。
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