MI-136 |
| Katalog-Nr.GC11837 |
MI-136 ist ein Inhibitor der Menin-MLL-Protein-Protein-Interaktion (PPI) mit einem IC50 von 31 nM und einem Kd von 23,6 nM. MI-136 blockiert offenbar die AR-SignalÜbertragung und hat das Potenzial fÜr die Studie bei kastrationsresistenten Tumoren.
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 |
| Löslichkeit | 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 |
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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.
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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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