store at low temperature,store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
MI-3454 is a highly potent, orally active, and selective inhibitor of the interaction between menin and MLL1, with an IC50 of 0.51 nM. This compound effectively inhibits the proliferation of leukemic cells and promotes their differentiation, leading to the regression or complete remission of leukemia in mouse models featuring MLL1 rearrangements or NPM1 mutations. This remarkable therapeutic effect is achieved through the downregulation of key genes involved in the development of leukemia.
产品描述 | MI-3454 is a highly potent, orally active, and selective inhibitor of the interaction between menin and MLL1, with an IC50 of 0.51 nM. This compound effectively inhibits the proliferation of leukemic cells and promotes their differentiation, leading to the regression or complete remission of leukemia in mouse models featuring MLL1 rearrangements or NPM1 mutations. This remarkable therapeutic effect is achieved through the downregulation of key genes involved in the development of leukemia. |
靶点活性 | Menin-MLL1:0.51 nM (IC50) |
体外活性 | MI-3454 (0.001-10 μM; 7 days) strongly reduces murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 proliferation[1]. 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[1]. MI-3454 markedly reduces the viability of leukemic cells harboring various MLL fusion proteins (MLL-AF9, MLL-AF4, MLL-ENL), with GI 50 values ranging from 7 to 27 nM. MI-3454 blocks the interaction of menin with an MLL1 4–43 fragment encompassing the entire menin binding motif[1]. MI-3454 does not potently inhibit cytochromes P450 (<50% inhibition at 10 μM)[1]. Cell Proliferation Assay[1]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[1]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 . |
体内活性 | 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[1]. MI-3454 (p.o.; 120 mg/kg; one or twice daily for 7 consecutive days) sufficiently blocks leukemia progression by a once-daily treatment[1]. 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[1]. 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[1]. MI-3454 exhibits favorable stability in murine and human liver microsomes (t 1/2 =20.4 minutes and 37.1 minutes, respectively)[1]. MI-3454 demonstrates lower levels in brain and cerebrospinal fluid, suggesting limited ability to cross the blood-brain barrier[1]. Animal Model: 8- to 10-week-old female NSG mice (MV-4-11 xenotransplantation model of MLL leukemia)[1]Dosage: 120 mg/kg Administration: Orally; one or twice daily for 7 consecutive days Result: A once-daily treatment was sufficient to block leukemia progression. Animal Model: Female CD-1 mice[1]Dosage: 100 mg/kg (PO) or 15 mg/kg (IV) (Pharmacokinetic Analysis) Administration: PO or IV Result: Had a T 1/2 of 3.2 hours, a C max of 4698 mg/mL for PO. Had a T 1/2 of 2.4 hours, a CL of 2375 mL/hours?kg, and a V ss of 5358 mL/kg for IV. |
分子量 | 636.74 |
分子式 | C32H35F3N8OS |
CAS No. | 2134169-43-8 |
store at low temperature,store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
MI-3454 2134169-43-8 MI3454 MI 3454 Inhibitor inhibitor inhibit