MI-3454

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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 IC50 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.

Cell Proliferation Assay Cell Line:Murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 Concentration:0.001, 0.01, 0.1, 1, 10 μM Incubation Time:7 days Result:Demonstrated strong reduction of cell proliferation.RT-PCR Cell Line:Human leukemic cell lines MV-4-11 cells or MOLM13 Concentration:50 nM Incubation Time:6 days Result:Led to downregulated expression of HOXA9 and MEIS1 and expression level of other MLL fusion target genes, including MEF2C, DLX2, HOXA10, PBX3, and FLT3.

Animal Model:8- to 10-week-old female NSG mice (MV-4-11 xenotransplantation model of MLL leukemia) Dosage:120 mg/kg Administration:Orally; one or twice daily for 7 consecutive daysResult:A once-daily treatment was sufficient to block leukemia progression. Animal Model:Female CD-1 mice Dosage:100 mg/kg (PO) or 15 mg/kg (IV) (Pharmacokinetic Analysis) Administration:PO or IV Result:Had a T1/2 of 3.2 hours, a Cmax of 4698 mg/mL for PO. Had a T1/2 of 2.4 hours, a CL of 2375 mL/hours?kg, and a Vss of 5358 mL/kg for IV.

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Others

Other Targets

Histone Methyltransferase

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2134169-43-8

636.73

C32H35F3N8OS

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 31.25 mg/mL (49.08 mM; 超声助溶 )

CNc1nc(NC2CCN(Cc3ccc4n(CC56CC(C5)(C6)NC=O)c(cc4c3C)C#N)CC2)c2cc(CC(F)(F)F)sc2n1

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(-20℃)

With Ice Pack

≥ 2 years