| CAS NO: | 1628317-18-9 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| Molecular Weight (MW) | 484.54 |
|---|---|
| Formula | C24H23F3N6S |
| CAS No. | 1628317-18-9 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 96 mg/mL (198.1 mM) |
| Water: <1 mg/mL | |
| Ethanol: 22 mg/mL (45.4 mM) | |
| Other info | Chemical Name: 4-methyl-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile InChi Key: DZACSLYTXLZAAF-UHFFFAOYSA-N InChi Code: InChI=1S/C24H23F3N6S/c1-14-15(2-3-21-19(14)8-17(11-28)31-21)12-33-6-4-16(5-7-33)32-22-20-9-18(10-24(25,26)27)34-23(20)30-13-29-22/h2-3,8-9,13,16,31H,4-7,10,12H2,1H3,(H,29,30,32) SMILES Code: CC1=C2C(NC(C#N)=C2)=CC=C1CN(CC3)CCC3NC4=C(C=C(CC(F)(F)F)S5)C5=NC=N4 |
| Synonyms | MI-463; MI 463; MI463. |
| In Vitro | In vitro activity: MI-463 can reach the target protein in mammalian cells and effectively inhibit the menin-MLL-AF9 interaction at sub-micromolar concentrations. Treatment of murine bone marrow cells (BMC) transformed with the MLL-AF9 oncogene with MI-463 results in substantial growth inhibition, with GI50 of 0.23 μM. Cell Assay: Leukemia cells are treated with MI-463 or 0.25% DMSO and cultured at 37 °C for 7 days. Media is changed at day 4, viable cell numbers are restored to the original concentration and MI-463 are re-supplied. MTT cell proliferation assay kit is then employed, and plates are read for absorbance at 570 nm using a microplate reader |
|---|---|
| In Vivo | MI-463 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (45%). Pharmacologic inhibition of the menin-MLL interaction substantially delays progression of MLL leukemia in murine models through on-target activity without causing toxicity. 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, are significant reduced upon treatment with MI-463. 20 days treatment of MV4;11 xenograft recipient mice with MI-463 also results in a substantial delay in leukemia progression as manifested by a marked decrease in the bioluminescence level which is associated with a significant decrease in the population of leukemic cells in the peripheral blood, spleen and bone marrow samples. |
| Animal model | Mice |
| Formulation & Dosage | i.p. administration |
| References | Cancer Cell. 2015 Apr 13;27(4):589-602. |
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