| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary target of MM-589 is WDR5 (WD repeat domain 5), functioning by blocking the interaction between WDR5 and MLL (mixed lineage leukemia) proteins. WDR5 is a core component of the H3K4 histone methyltransferase complex, interacting with MLL1-MLL4 family members and playing a key role in histone H3K4 trimethylation, chromatin remodeling, and transcriptional activation of target genes. MM-589 binds to WDR5 with high affinity, competitively occupying the MLL binding interface, thereby specifically inhibiting MLL1 methyltransferase activity without affecting other MLL family members.
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| ln Vitro |
Human leukemia cell lines with the MLL translocation exhibit a potent and selective inhibition of cell growth when exposed to MM-589 (0.01-10 µM) for 4 or 7 days [1].
MM-589 exhibits excellent inhibitory activity in vitro. By fluorescence polarization competition assay, MM-589 binds to WDR5 with an IC₅₀ of 0.90 nM (Ki < 1 nM); in a fully reconstituted MLL core complex (MLL1-WDR5-RbBP5-ASH2L) histone methyltransferase (HMT) assay, it inhibits with an IC₅₀ of 12.7 nM. In MLL-rearranged human leukemia cell lines (e.g., MLL-AF9, MLL-ENL), MM-589 potently and selectively inhibits cell proliferation, demonstrating >40-fold improved potency compared to MM-401. MM-589 treatment significantly reduces H3K4me3 levels and downregulates expression of MLL target genes such as HOXA9 and MEIS1. |
| ln Vivo |
MM-589 demonstrates in vivo anti-leukemic activity in animal models. MM-589 derivatives administered by intravenous injection effectively suppress tumor cell expansion and prolong survival in mouse models of MLL leukemia. Studies indicate that MLL-WDR5 interaction inhibitor derivatives with improved pharmacokinetic properties have the potential to be trialed in cancer patients. Compared to MM-401, MM-589 exhibits superior pharmacodynamic profiles in in vivo studies due to its improved cellular permeability and metabolic stability. No significant toxicity to normal hematopoietic function has been observed during treatment.
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| Enzyme Assay |
WDR5 Protein Expression and Purification: Express recombinant human WDR5 protein in E. coli and purify by affinity chromatography and size-exclusion chromatography.
Fluorescence Polarization Competition Assay: Incubate WDR5 protein with fluorescently labeled MLL-derived peptide (FAM-labeled WIN peptide) and varying concentrations of MM-589, measure changes in fluorescence polarization. MM-589 binds to WDR5 with an IC₅₀ of 0.90 nM (Ki < 1 nM).
In Vitro MLL HMT Functional Assay: Use AlphaLISA or scintillation counting methods. Pre-incubate the reconstituted MLL core complex (MLL1-WDR5-ASH2L-RbBP5) with varying concentrations of MM-589, add histone H3 substrate and [³H]-SAM to initiate the reaction, measure [³H]-methyl incorporation. The IC₅₀ for HMT activity inhibition is 12.7 nM.
Co-crystallization Structure Determination: Mix WDR5 and MM-589 at a 1:2 molar ratio, crystallize by hanging-drop vapor diffusion method, and determine the co-crystal structure at 1.64 Å resolution (PDB: 5VFC).
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| Cell Assay |
Cell viability assay [1]
Cell Types: MV4-11 and MOLM-13 Cell Tested Concentrations: 0.01, 0.1, 1, 10 μM Incubation Duration: 4 days or 7 days Experimental Results: Effectively inhibits the growth of MV4-11 and MOLM-13 cells, IC50 The values are 0.25 and 0.21 μM respectively. The inhibitory activity on the cell growth of HL-60 cell line is weak, with IC50 of 8.6 μM. Cell Culture: Culture MLL-rearranged leukemia cell lines (e.g., MLL-AF9-transduced cells, MV4-11, KOPN-8) and non-MLL leukemia cells (e.g., K562, HL60, U937) in RPMI-1640 medium with 10% fetal bovine serum at 37°C, 5% CO₂. Cell Proliferation Assay: Seed cells in 96-well plates (1×10⁵/mL), treat with varying concentrations of MM-589 (0-10 μM) or MM-401 as control, culture for 3-5 days, and measure cell viability using CellTiter-Glo or CCK-8 assays. Cell Cycle Analysis: After 48 hours of MM-589 treatment, fix cells with 70% ethanol, stain with PI, and analyze cell cycle distribution by flow cytometry. Apoptosis Detection: Detect apoptosis rate using Annexin V-FITC/PI double staining. Western Blot Analysis: Extract proteins to detect H3K4me3 levels and expression changes of target proteins such as HOXA9 and MEIS1. Data Analysis: MM-589 exhibits >40-fold improved growth inhibition potency against MLL-rearranged leukemia cells compared to MM-401. |
| Animal Protocol |
Animal Models: Establish disseminated leukemia models by intravenous injection of MLL-rearranged leukemia cells (e.g., MLL-AF9 cells) into immunodeficient mice (NSG or NOD/SCID mice) via the tail vein.
Dosing Regimen: Administer MM-589 by intravenous injection, typically once daily for 2-3 consecutive weeks. Due to the improved solubility of the TFA salt form of MM-589, it should be formulated in appropriate vehicle buffers.
Efficacy Assessment: Monitor tumor burden by bioluminescent imaging, record survival (Kaplan-Meier analysis), and detect the percentage of leukemia cells (hCD45⁺) in peripheral blood and bone marrow by flow cytometry.
Toxicity Assessment: Monitor animal body weight changes, behavioral performance, and peripheral blood cell counts to evaluate effects on normal hematopoietic function.
Pharmacodynamic Analysis: Collect bone marrow or spleen samples to detect H3K4me3 levels and target gene expression such as HOXA9.
Data Analysis: Compare survival differences and tumor burden changes between treatment and control groups.
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| ADME/Pharmacokinetics |
As a macrocyclic peptidomimetic, MM-589 exhibits significantly improved metabolic stability and cellular permeability through a cyclization strategy compared to the linear peptide MM-101. This compound has good solubility in DMSO. The TFA salt form has improved solubility in aqueous buffers, making it more suitable for in vivo administration. MM-589 powder is stable for 2-3 years when stored at -20°C or 4°C protected from light; solutions are stable for 6 months at -80°C protected from light. MM-589 represents the most potent inhibitor of the WDR5-MLL interaction reported to date, and further optimization may yield a new therapy for acute leukemia.
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| Toxicity/Toxicokinetics |
According to the Safety Data Sheet, MM-589 is not classified as a hazardous substance or mixture, and GHS label elements do not apply. Toxicological testing: Not listed as a carcinogen by NTP; not listed by IARC; not regulated by OSHA; not listed by ACGIH. At the cellular level, MM-589 shows no significant toxicity to normal bone marrow cells, selectively inhibiting the proliferation of MLL-rearranged leukemia cells. The toxicological effects of this product have not been thoroughly studied. Standard laboratory safety practices should be followed when handling, and release to the environment should be avoided. MM-589 has a purity of ≥98% and is for research use only, not for human or veterinary applications.
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| References |
| Molecular Formula |
C28H44N8O5
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|---|---|
| Molecular Weight |
572.699565887451
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| Exact Mass |
572.343
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| CAS # |
2097887-20-0
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| Related CAS # |
MM-589 TFA;2253167-09-6;MM-589 (racemic mixture ) (TFA)
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| PubChem CID |
129010138
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| Sequence |
isobutyryl-D-aMeDab(1)-Arg(Me)(Me)-Abu-D-Phg-(1)
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
0.6
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
41
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| Complexity |
965
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC[C@H]1C(=O)N[C@@H](C(=O)NCC[C@@](C(=O)N[C@H](C(=O)N1)CCCNC(=NC)N)(C)NC(=O)C(C)C)C2=CC=CC=C2
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| InChi Key |
ZAIPJVQTYUSDTG-LDFBIXNTSA-N
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| InChi Code |
InChI=1S/C28H44N8O5/c1-6-19-23(38)35-21(18-11-8-7-9-12-18)25(40)31-16-14-28(4,36-22(37)17(2)3)26(41)34-20(24(39)33-19)13-10-15-32-27(29)30-5/h7-9,11-12,17,19-21H,6,10,13-16H2,1-5H3,(H,31,40)(H,33,39)(H,34,41)(H,35,38)(H,36,37)(H3,29,30,32)/t19-,20-,21+,28+/m0/s1
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| Chemical Name |
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N'-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide
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| Synonyms |
MM-589; MM 589; MM589; 2097887-20-0; N-{(3r,6s,9s,12r)-6-Ethyl-12-Methyl-9-[3-(N'-Methylcarbamimidamido)propyl]-2,5,8,11-Tetraoxo-3-Phenyl-1,4,7,10-Tetraazacyclotetradecan-12-Yl}-2-Methylpropanamide; CHEMBL4116919; N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N'-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7461 mL | 8.7306 mL | 17.4611 mL | |
| 5 mM | 0.3492 mL | 1.7461 mL | 3.4922 mL | |
| 10 mM | 0.1746 mL | 0.8731 mL | 1.7461 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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