MI-3454

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

MI-3454  纯度: 99.79%

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

MI-3454 Chemical Structure

CAS No. : 2134169-43-8

规格 价格 是否有货 数量
5 mg ¥6200 In-stock
10 mg ¥9800 In-stock
50 mg   询价  
100 mg   询价  

* Please select Quantity before adding items.

MI-3454 相关产品

相关化合物库:

  • Covalent Screening Library Plus
  • Bioactive Compound Library Plus
  • Epigenetics Compound Library
  • Histone Modification Research Compound Library
  • Anti-Cancer Compound Library
  • Covalent Screening Library
  • Reprogramming Compound Library
  • Anti-Blood Cancer Compound Library
  • Targeted Diversity Library

生物活性

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[1].

IC50 & Target

IC50: 0.51 nM (menin-MLL1 interaction)[1]

体外研究
(In Vitro)

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 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[1].
MI-3454 does not potently inhibit cytochromes P450 (<50% inhibition at 10 μM)[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究
(In Vivo)

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 T1/2 of 3.2 hours, a Cmax of 4698 mg/mL for PO[1].
MI-3454 exhibits favorable stability in murine and human liver microsomes (t1/2=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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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 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.

分子量

636.73

Formula

C32H35F3N8OS

CAS 号

2134169-43-8

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, stored under nitrogen

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

溶解性数据
In Vitro: 

DMSO : 31.25 mg/mL (49.08 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.5705 mL 7.8526 mL 15.7052 mL
5 mM 0.3141 mL 1.5705 mL 3.1410 mL
10 mM 0.1571 mL 0.7853 mL 1.5705 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

参考文献
  • [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.

所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务