MI-3454 是一种具有口服活性，高效和选择性的 Menin-MLL1 相互作用抑制剂，IC₅₀ 为 0.51 nM。MI-3454 通过下调涉及白血病发生的关键基因，在 MLL1 重排或 NPM1 突变的白血病小鼠模型中抑制细胞增殖，诱导分化并完全缓解或消退白血病。

MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC 50 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.

Solid

IC50: 0.51 nM (menin-MLL1 interaction)

MI-3454 (0.001-10 μM; 7 days) strongly reduces murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 proliferation.
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.
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.
MI-3454 does not potently inhibit cytochromes P450 (<50% inhibition at 10 μM).
has not independently confirmed the accuracy of these methods. They are for reference only.

MI-3454 induces complete remission or regression of leukemia in mouse models of mixed lineage leukemia 1 (MLL1)-rearranged or nucleophosmin 1 (NPM1)-mutated leukemia.
MI-3454 (p.o.; 120 mg/kg; one or twice daily for 7 consecutive days) sufficiently blocks leukemia progression by a once-daily treatment.
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.
MI-3454 (100 mg/kg of PO or 15 mg/kg of IV) has a T 1/2 of 3.2 hours, a C max of 4698 mg/mL for PO.
MI-3454 exhibits favorable stability in murine and human liver microsomes (t 1/2 =20.4 minutes a

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

[1]. Szymon Klossowski, et al. Menin Inhibitor MI-3454 Induces Remission in MLL1-rearranged and NPM1-mutated Models of Leukemia. J Clin Invest. 2020 Feb 3;130(2):981-997.

In Vitro: DMSO : 31.25 mg/mL (49.08 mM; Need ultrasonic)配制储备液