MI-136
目录号 : GC11837
A menin-MLL inhibitor
Cas No.:1628316-74-4
Sample solution is provided at 25 µL, 10mM.
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IC50: 31 nM
MI-136 is a menin-MLL interaction inhibitor.
Chromosomal translocations regulating mixed lineage leukemia gene (MLL) can result in the acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion protein is reported to be dependent on its interactions with menin, providing the basis for therapeutic intervention.
In vitro: MI-136 was found to be able to strongly bind to menin with Kd of 24 nM, potently inhibit menin interaction with MLL, and block proliferation of MLL leukemia cells at submicromolar concentrations (GI50 = 0.55 μM in the MLL-AF9 cells), indicating that MI-136 represented a valuable pharmacophore for menin-MLL inhibitors. In addition, MI-136 did not show substantial off-target activity when profiled on a panel of kinases and GPCRs [1].
In vivo: Animal study showed that treatment of VCaP tumor–bearing mice with MI-136 at 40 mg/kg resulted in a modest but significant reduction in tumor volume when compared to vehicle treatment with no effect on body weight of mouse. These data demonstrated that the pharmacologic inhibition of the menin-MLL interaction was an effective in vivo treatment for MLL leukemias and provided advanced molecular scaffold for clinical lead identification [2].
Clinical trial: Up to now, MI-136 is still in the preclinical development stage.
References:
1. D. Borkin, J. Pollock, K. Kempinska,et al.Property focused structure-based optimization of small molecule inhibitors of the protein-protein interaction between menin and mixed lineage leukemia (MLL). Journal of Medicinal Chemistry 59(3),892-913(2016).
2. R. Malik, A. P. Khan, I. A. Asangani,et al. Targeting the MLL complex in castration-resistant prostate cancer.Nat. Med.21(4),344-352(2015).
| Cas No. | 1628316-74-4 | SDF | |
| 化学名 | 5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile | ||
| Canonical SMILES | N#CC(N1)=CC2=C1C=CC(CN3CCC(NC4=C(C=C(CC(F)(F)F)S5)C5=NC=N4)CC3)=C2 | ||
| 分子式 | C23H21F3N6S | 分子量 | 470.51 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,Ethanol: 10 mg/ml | 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 | 2.1254 mL | 10.6268 mL | 21.2535 mL |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2507 mL |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 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
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet