MM-102 (Synonyms: HMTase Inhibitor IX) |
| Catalog No.GC14652 |
MM-102 (HMTase Inhibitor IX) es un potente inhibidor de la interacciÓn WDR5/MLL, alcanza IC50= 2,4 nM con una Ki estimada en 200 veces mÁs potente que el péptido ARA.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1417329-24-8
Sample solution is provided at 25 µL, 10mM.
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MM-102 is an antagonist of MLL1 with IC50 value of 2.4nM [1].
Mixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase. The interaction of MLL1 and WDR5 is essential for MLL1 enzymatic activity and is a target for the treatment of acute leukemia. MM-102 is a peptidomimetic of MLL1. It has a high binding affinity to WDR5 with IC50 value of 2.4nM [1].
MM-102 is reported to reduce the expression of MLL1 targeted genes HoxA9 and Meis-1 in MLL1-AF9 transduced murine cells. Since these two genes are required for MLL1 mediated leukemogenesis, MM-102 is found to inhibit cell growth of leukemia cells harboring MLL1 fusion proteins. It dose-dependently inhibits the cell growth in the MV4;11 and KOPN8 cell lines with IC50 values both of 25μM[1].
References:
[1] Karatas H, Townsend EC, Cao F, Chen Y, Bernard D, Liu L, Lei M, Dou Y, Wang S. High-affinity, small-molecule peptidomimetic inhibitors of MLL1/WDR5 protein-protein interaction. J Am Chem Soc. 2013 Jan 16;135(2):669-82.
| Kinase experiment [1]: | |
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In Vitro Histone Methyltransferase (HMT) Assay |
The HMT assay is performed in 50 mM HEPES pH 7.8, 100 mM NaCl, 1.0 mM EDTA, and 5% glycerol at 22 °C. Each reaction contains 1.5 μCi of the co-factor, 3H-S-adenosylmethionine. H3 10-residue peptide is used as the substrate at 50 μM. Compounds are added at concentrations ranging from 0.125 to 128 μM and incubated with the pre-assembled WDR5/RbBP5/ASH2L complex at a final concentration of 0.5 μM for each protein for 2–5 min. Reactions are initiated by addition of the MLL1 protein at a final concentration of 0.5 μM and allowed to proceed for 30 min before preparing scintillation counting. To count samples, reactions are spotted on separate squares of P81 filter paper and precipitated by submerging in freshly prepared 50 mM sodium bicarbonate buffer with pH 9.0. After washing and drying, samples are vortexed in Ultima Gold scintillation fluid and counted. As a negative control, assays are performed using 0.5 μM MLL1/WDR5/RbBP5/ASH2L complex assembled with the non-interacting mutant, WDR5D107A. |
| Cell experiment [1]: | |
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Cell lines |
MV4-11 cells, KOPN8, and K562 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
6.25, 25, 50 μM for 4-7 days; |
|
Applications |
MM-102 significantly inhibited the expression of HoxA9 and Meis-1, two critical MLL1 target genes in MLL1 fusion protein mediated leukemogenesis. MM-102 (6.25, 25, 50 μM) also specifically suppressed cell growth and induced apoptosis in leukemia cells harboring MLL1 fusion proteins. |
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References: [1]H. Karatas, E.C. Townsend, F. Cao, Y. Chen, D. Bernard, L. Liu, M. Lei, Y. Dou, S. Wang, High-affinity, small-molecule peptidomimetic inhibitors of MLL1/WDR5 protein-protein interaction. J Am Chem Soc 135 (2013) 669-682. | |
| Cas No. | 1417329-24-8 | SDF | |
| Sinónimos | HMTase Inhibitor IX | ||
| Chemical Name | N-[bis(4-fluorophenyl)methyl]-1-[[(2S)-5-(diaminomethylideneamino)-2-[[2-ethyl-2-(2-methylpropanoylamino)butanoyl]amino]pentanoyl]amino]cyclopentane-1-carboxamide | ||
| Canonical SMILES | CCC(CC)(C(=O)NC(CCCN=C(N)N)C(=O)NC1(CCCC1)C(=O)NC(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F)NC(=O)C(C)C | ||
| Formula | C35H49F2N7O4 | M.Wt | 669.8 |
| Solubility | ≥ 67mg/mL in DMSO | 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 | 1.493 mL | 7.4649 mL | 14.9298 mL |
| 5 mM | 0.2986 mL | 1.493 mL | 2.986 mL |
| 10 mM | 0.1493 mL | 0.7465 mL | 1.493 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 18 reference(s) in Google Scholar.)
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