MI-3454|cas:2134169-43-8|西域试剂

MI-3454,99.68%

产品编号：Bellancom-136360| CAS NO：2134169-43-8| 分子式：C₃₂H₃₅F₃N₈OS| 分子量：636.73

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货号	包装	价格	库存与货期	购买量	操作
Bellancom-136360		￥6200.00	杭州北京（现货）
Bellancom-136360		￥9800.00	杭州北京（现货）

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MI-3454

产品介绍

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。

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.

体外研究

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 MLL1_4–43 fragment encompassing the entire menin binding motif.
MI-3454 does not potently inhibit cytochromes P450 (<50% inhibition at 10 μM).

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

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.
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 and 37.1 minutes, respectively).
MI-3454 demonstrates lower levels in brain and cerebrospinal fluid, suggesting limited ability to cross the blood-brain barrier.

西域 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)
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
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.

体内研究

西域 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)
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
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.

体内研究

西域 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)
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
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.

性状

Solid

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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶