| Name | MI-463 |
| Description | MI-463 is a potent and orally bioavailable inhibitor of the menin-mLL interaction (IC50: 15.3 nM). |
| Cell Research | Leukemia cells are treated with MI-463 or 0.25% DMSO and cultured at 37 °C for 7 days. Media is changed on day 4, viable cell numbers are restored to the original concentration and MI-463 is re-supplied. MTT cell proliferation assay kit is then employed, and plates are read for absorbance at 570 nm using a microplate reader. |
| Animal Research | For efficacy studies in MV4;11 subcutaneous xenograft mice model, 5×10^6 cells are injected into the 4-6 week old female BALB/c nude mice. Treatment is started when the tumor size reached ~100 mm^3. Vehicle (25% DMSO, 25% PEG400, 50% PBS) or MI-463 are administrated once daily at designated doses using i.p. injections. |
| In vitro | Treatment of murine bone marrow cells (BMC) transformed with the mLL-AF9 oncogene with MI-463 results in substantial growth inhibition (GI50: 0.23 μM). MI-463 is effective in inducing differentiation of MLL leukemia cells. Treatment with sub-micromolar concentrations of MI-463 also leads to markedly reduced expression of Hoxa9 and Meis1. |
| In vivo | MI-463 shows substantial survival benefit in mouse models of MLL leukemia. It has very favorable druglike properties, including metabolic stability and PK profile in mice. MI-463 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (45%). MI-463 induces strong inhibition of tumor growth with once-daily intraperitoneal (i.p.) administration. The expression of mLL fusion protein target genes, HOXA9 and MEIS1, is significantly reduced upon treatment with MI-463. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 120 mg/mL (247.66 mM), Sonication is recommended.
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| Keywords | Epigenetic Reader Domain | Inhibitor | MI 463 | MI-463 | inhibit | MI463 |
| Inhibitors Related | ABBV-744 | 3-methyl-1,2,3,4-tetrahydroquinazolin-2-one | (+)-JQ-1 | Tazemetostat | Piribedil | GSK126 | Curcumin | EPZ015666 | dBET6 | Naphthol AS-E | MRTX-1719 | Bisdemethoxycurcumin |
| Related Compound Libraries | Bioactive Compound Library | Epigenetics Compound Library | Chromatin Modification Compound Library | Inhibitor Library | NO PAINS Compound Library | Orally Active Compound Library | PPI Inhibitor Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Covalent Inhibitor Library |
United States
