MI-463

SKU: orb1296237

Description

MI-463 is a potent, orally bioavailable small molecule inhibitor of the menin-MLL protein-protein interaction, exhibiting an IC50 of 15.3 nM. It is a valuable chemical probe for researching MLL-rearranged leukemias in both cellular assays and in vivo models.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1628317-18-9
• MW: 484.54
• Purity: >99.99% (May vary between batches)
• Formula: C₂₄H₂₃F₃N₆S
• SMILES: Cc1c(CN2CCC(CC2)Nc2ncnc3sc(CC(F)(F)F)cc23)ccc2[nH]c(cc12)C#N
• Target: Histone Methyltransferase,Epigenetic Reader Domain
• Solubility: DMSO:120 mg/mL (247.66 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (8.26 mM)

Bioactivity

• 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.
• 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.
• 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, Menin-MLL, Histone Methyltransferase, HistoneMethyltransferase, Epigenetic Reader Domain, EpigeneticReaderDomain, inhibit, MI 463, MI463, MI-463

Compound Identifiers

PubChem CID

90455046