MI-136 |
| Catalog No.GC11837 |
MI-136은 IC50이 31nM이고 Kd가 23.6nM인 메닌-MLL 단백질-단백질 상호작용(PPI)의 억제제입니다. MI-136은 AR 신호 전달을 차단하는 것으로 나타났으며 거세 저항성 종양에 대한 연구 가능성이 있습니다.
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Chemical Name | 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 | ||
| Formula | C23H21F3N6S | M.Wt | 470.51 |
| Solubility | DMF: 1 mg/ml,DMSO: 1 mg/ml,Ethanol: 10 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 15 reference(s) in Google Scholar.)
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