MI-2
MI-2 (CAS 1271738-62-5) is a small molecule inhibitor targeting the menin-MLL protein-protein interaction, with an IC50 of 0.45 μM. The formation of menin-MLL fusion protein complexes, resulting from chromosomal rearrangements, plays an essential role in the pathogenesis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). MI-2 selectively binds wild-type menin, disrupting its interaction with MLL-fusion proteins such as MLL-AF9, thereby inhibiting cellular proliferation and colony formation in MLL-AF9-transduced mouse bone marrow cells. MI-2 serves as a research tool in studies of leukemia biology and menin-associated oncogenesis.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 375.55 |
| Cas No. | 1271738-62-5 |
| Formula | C18H25N5S2 |
| Synonyms | Menin-MLL inhibitor 2;Thieno[2,3-d]pyrimidine, 4-[4-(4,5-dihydro-5,5-dimethyl-2-thiazolyl)-1-piperazinyl]-6-propyl- |
| Solubility | insoluble in H2O; ≥15.1 mg/mL in DMSO; ≥46.4 mg/mL in EtOH with gentle warming |
| Chemical Name | 4-[4-(5,5-dimethyl-4H-1,3-thiazol-2-yl)piperazin-1-yl]-6-propylthieno[2,3-d]pyrimidine |
| SDF | Download SDF |
| Canonical SMILES | CCCC1=CC2=C(N=CN=C2S1)N3CCN(CC3)C4=NCC(S4)(C)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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High throughput screening |
FITC-MBM1 at 15 nM and Menin at 150 nM in the FP buffer were mixed and incubated for 1hr in the dark at room temperature. For point screening, the 0.2 μL of each compound (20 μM final concentration, 1% DMSO) was added to 20 μL of the aliquot of the protein-peptide mixture and incubated on 384-well plates in the dark at room temperature for 1hr. In confirmation screening, the serial dilution plates with compounds in DMSO were prepared and used to titrate the Menin-FITC-MBM1 complex. Change in fluorescence polarization was monitored at 525 nm after excitations at 495 nm using the PHERAstar microplate reader (BMG) and applied to determine IC50 values with the Origin 7.0 program. |
| Cell experiment [1]: | |
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Cell lines |
MLL-AF9 and MLL-ENL transduced murine BMCs |
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Preparation method |
The solubility of this compound in DMSO is > 15.1 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
3 ~ 25 μM |
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Applications |
In MLL-AF9 and MLL-ENL transduced murine BMCs, MI-2 inhibited the proliferation of BMCs with a GI50 value of about 5 μM. Moreover, MI-2 reduced colony formation in BMCs transduced with MLL-AF9. In a series of human MLL leukemia cell lines with different MLL translocations, MI-2 significantly inhibited cell proliferation and induced cell apoptosis. |
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References: [1]. Grembecka J, He S, Shi A, et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol, 2012, 8(3): 277-284. |
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Quality Control & MSDS
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Chemical structure
