MI-503
目录号 : GC19247
MI-503 是一种高效且具有口服生物利用度的 menin-mLL 相互作用的小分子抑制剂。
Cas No.:1857417-13-0
Sample solution is provided at 25 µL, 10mM.
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MI-503 is a highly potent and orally bioavailable small molecule inhibitor of the menin-mLL interaction.
MI-503 occupies the F9 and P13 pockets on menin, forming a hydrogen bond with Tyr276, and also extends beyond the P13 pocket to form hydrogen bonds with Trp341 and Glu366. Treatment of murine bone marrow cells (BMC) transformed with the mLL-AF9 oncogene with MI-503 results in substantial growth inhibition, with GI50 of 0.22 uM. The cell growth inhibitory effect of MI-503 is time-dependent, with a pronounced effect achieved after 7-10 days of treatment[1].
MI-503 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (75%). MI-503 induces strong inhibition of tumor growth with once daily intraperitoneal (i.p.) administration. Treatment with MI-503 results in an over 80% reduction in MV4;11 tumor volume and complete tumor regression in two mice. Ten consecutive days of treatment with MI-503 results in a marked delay in progression of mLL leukemia in mice and significantly reduces leukemia tumor burden. Treatment with MI-503 and MI-463 leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of mLL fusion proteins substantially upregulated in mLL leukemias[1].
References:
[1]. Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr 13;27(4):589-602.
Cell experiment: | Leukemia cells are treated with MI-503 or 0.25% DMSO and cultured at 37 °C for 7 days. Media is changed at day 4, viable cell numbers are restored to the original concentration and MI-503 are re-supplied. MTT cell proliferation assay kit is then employed, and plates are read for absorbance at 570 nm using a microplate reader[1]. |
Animal experiment: | Mice: For efficacy studies in MV4;11 subcutaneous xenograft mice model, 5×106 cells are injected into the 4-6 week old female BALB/c nude mice. Treatment is started when the tumor size reached ~100 mm3. Vehicle (25% DMSO, 25% PEG400, 50% PBS) or compounds (MI-463 or MI-503) are administrated once daily at designated doses using i.p. injections[1]. |
References: [1]. Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr 13;27(4):589-602. | |
| Cas No. | 1857417-13-0 | SDF | |
| Canonical SMILES | FC(F)(F)CC(S1)=CC2=C1N=CN=C2NC3CCN(CC4=CC=C(N(CC5=CNN=C5)C(C#N)=C6)C6=C4C)CC3 | ||
| 分子式 | C28H27F3N8S | 分子量 | 564.63 |
| 溶解度 | DMSO : 50 mg/mL (88.55 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7711 mL | 8.8554 mL | 17.7107 mL |
| 5 mM | 0.3542 mL | 1.7711 mL | 3.5421 mL |
| 10 mM | 0.1771 mL | 0.8855 mL | 1.7711 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet