MI-3454
Based on 3 publication(s) in Google Scholar
MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC50 of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia through downregulation of key genes involved in leukemogenesis.
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- Purity: 98.03%
- CAS No.: 2134169-43-8
- 화학식: C32H35F3N8OS
- 분자량:636.73
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보관:
4°C, stored under nitrogen
* In solvent : -80°C, 2 years; -20°C, 1 year (stored under nitrogen)
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) MI-3454
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Biological Activity
IC50: 0.51 nM (menin-MLL1 interaction)[1]
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Cell Line
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Type | Value | Description | References |
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| MOLM-13 | GI50 |
12.5 nM
Compound: 7; MI-3454
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Antiproliferative activity against human MOLM-13 cells
Antiproliferative activity against human MOLM-13 cells
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[PMID: 34726905] |
| MV4-11 | GI50 |
7.6 nM
Compound: 7; MI-3454
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Antiproliferative activity against human MV4-11 cells
Antiproliferative activity against human MV4-11 cells
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[PMID: 34726905] |
MI-3454 (0.001-10 μM; 7 days) strongly reduces murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 proliferation[1].
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MI-3454 (50 nM; 6 days) leads to downregulated expression of HOXA9 and MEIS1 in Human leukemic cell lines MV-4-11 cells or MOLM13[1].
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MI-3454 markedly reduces the viability of leukemic cells harboring various MLL fusion proteins (MLL-AF9, MLL-AF4, MLL-ENL), with GI50 values ranging from 7 to 27 nM. MI-3454 blocks the interaction of menin with an MLL14–43 fragment encompassing the entire menin binding motif[1].
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MI-3454 does not potently inhibit cytochromes P450 (<50% inhibition at 10 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1
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Concentration:0.001, 0.01, 0.1, 1, 10 μM
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Incubation Time:7 days
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Result:Demonstrated strong reduction of cell proliferation.
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Cell Line:Human leukemic cell lines MV-4-11 cells or MOLM13
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Concentration:50 nM
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Incubation Time:6 days
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Result:Led to downregulated expression of HOXA9 and MEIS1 and expression level of other MLL fusion target genes, including MEF2C, DLX2, HOXA10, PBX3, and FLT3.
? MI-3454 (p.o.; 120 mg/kg; one or twice daily for 7 consecutive days) sufficiently blocks leukemia progression by a once-daily treatment[1].
? MI-3454 (p.o.; 100 mg/kg; b.i.d.; for 19 consecutive days) effectively blocks leukemia progression during the treatment period and markedly prolongs survival of MOLM13 xenotransplantation model mice. MI-3454 induces complete remission or blocks leukemia progression in patient-derived xenograft (PDX) models of MLL leukemia[1].
? MI-3454 (100 mg/kg of PO or 15 mg/kg of IV) has a T1/2 of 3.2 hours, a Cmax of 4698 mg/mL for PO[1].
? MI-3454 exhibits favorable stability in murine and human liver microsomes (t1/2=20.4 minutes and 37.1 minutes, respectively)[1].
? MI-3454 demonstrates lower levels in brain and cerebrospinal fluid, suggesting limited ability to cross the blood-brain barrier[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:8- to 10-week-old female NSG mice (MV-4-11 xenotransplantation model of MLL leukemia)[1]
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Dosage:120 mg/kg
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Administration:Orally; one or twice daily for 7 consecutive days
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Result:A once-daily treatment was sufficient to block leukemia progression.
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Animal Model:Female CD-1 mice[1]
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Dosage:100 mg/kg (PO) or 15 mg/kg (IV) (Pharmacokinetic Analysis)
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Administration:PO or IV
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Result:Had a T1/2 of 3.2 hours, a Cmax of 4698 mg/mL for PO.
Had a T1/2 of 2.4 hours, a CL of 2375 mL/hours•kg, and a Vss of 5358 mL/kg for IV.
Chemical Information
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CAS No. 2134169-43-8
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Appearance Solid
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분자량 636.73
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화학식 C32H35F3N8OS
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Color Light brown to brown
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SMILES
O=CNC1(C2)CC2(CN3C(C#N)=CC4=C3C=CC(CN5CCC(NC6=C(C=C(CC(F)(F)F)S7)C7=NC(NC)=N6)CC5)=C4C)C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
4°C, stored under nitrogen
* In solvent : -80°C, 2 years; -20°C, 1 year (stored under nitrogen)
Publications (3)
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Journal Impact Factor
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Most Recent
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BMC Med
Epigenetic drug screening for trophoblast syncytialization reveals a novel role for MLL1 in regulating fetoplacental growth. [Abstract]2024 Feb 5;22(1):57. PMID: 38317232 -
iScience
2021 Dec 25;25(1):103679. PMID: 35036869 -
용액&용해도
DMSO : 31.25 mg/mL (49.08 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (stored under nitrogen). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (stored under nitrogen). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 20% DMSO 20% Cremophor EL 60% Saline
Solubility: 5 mg/mL (7.85 mM); Suspended solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 2 years; -20°C, 1 year (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (278 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (stored under nitrogen). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.5705 mL | 7.8526 mL | 15.7052 mL | 39.2631 mL |
| 5 mM | 0.3141 mL | 1.5705 mL | 3.1410 mL | 7.8526 mL | |
| 10 mM | 0.1571 mL | 0.7853 mL | 1.5705 mL | 3.9263 mL | |
| 15 mM | 0.1047 mL | 0.5235 mL | 1.0470 mL | 2.6175 mL | |
| 20 mM | 0.0785 mL | 0.3926 mL | 0.7853 mL | 1.9632 mL | |
| 25 mM | 0.0628 mL | 0.3141 mL | 0.6282 mL | 1.5705 mL | |
| 30 mM | 0.0524 mL | 0.2618 mL | 0.5235 mL | 1.3088 mL | |
| 40 mM | 0.0393 mL | 0.1963 mL | 0.3926 mL | 0.9816 mL |
MI-3454 Related Classifications
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