MIM1
(Synonyms: 4-[[[2-(环己基亚氨基)-4-甲基-3(2H)-噻唑基]亚氨基]甲基]-1,2,3-苯三醇,Inhibitor of Mcl-1) 目录号 : GC15400
An Mcl-1 inhibiting molecule
Cas No.:509102-00-5
Sample solution is provided at 25 µL, 10mM.
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MIM1 effectively competed with FITC-MCL-1 SAHBA and FITC-BID BH3 for MCL-1ΔNΔC binding with IC50 values of 4.7 and 4.8 mM, respectively. And MIN1 shows a combination of favorable biophysical and biological properties including its solubility, stability, nonreactivity, MCL-1 binding potency and selectivity, compatibility with and activity in a BAX-mediated liposomal release assay and relatively little to no toxicity in Bax-/-Bak-/- MEFs [1].
As an MCL-1 inhibitor, MIM1 selectively targets the BH3-binding groove of MCL-1, neutralizes its biochemical lockhold on apoptosis, and induces caspase activation and leukemia cell death in the specific context of MCL-1 dependence.
The activity and specificity of MIM1 in cancer cells was dependable for assessing MCL-1 and BCL-XL dependence by employing murine BCRABL (p185)-transformed, Arf null, B-lineage acute lymphoblastic leukemia cells. Comparing to the effect of ABT-737 on p185+Arf-/-/Mcl-1-deleted B-ALL cells, MIM1 had the exact opposite effect, impacting the viability of the MCL-1-dependent cells (IC50, 4.2 mM), including dose-dependent induction of caspase 3/7 activity, but having no effect on the BCL-XL-dependent cells. A combination of MIM1 (IC50, 10.6 mM) and ABT-737 (IC50, 5.1 mM) resulted in synergistic cytotoxicity. Strikingly, when the MIM1/ABT-737 combination was applied to MCL-1-reconstituted p185+Arf-/-/Mcl-1-deleted B-ALL cells, the addition of ABT-737 had little effect [1].
MIM1 emerged as a potent and selective small molecule inhibitor of MCL-1 DNDC, capable of targeting the canonical BH3-binding point of MCL-1 and blocking MCL-1-mediated suppression of tBID-induced BAX activation in vitro. MIM1 may serve as a prototype for the development of next generation small molecules that effectively reduce the apoptotic threshold in cancers specifically driven by antiapoptotic MCL-1 [1].
Reference:
[1]. Cohen NA, Stewart ML, Gavathiotis E, et al. A Competitive Stapled Peptide Screen Identifies a Selective Small Molecule that Overcomes MCL-1-Dependent Leukemia Cell Survival. Chemistry & Biology, 2012, 19(9): 1175-1186.
| Cell experiment: [1] | |
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Cell lines |
p185+Arf−/−Mcl-1-deleted B-ALL cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
IC50: 4.2 μM, 24 hours for impairing the cell viability rescued by MCL-1 |
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Applications |
MIM1 negatively impacted the viability of the MCL-1-dependent cells (p185+Arf−/−Mcl-1-deleted B-ALL cells) with IC50 value of 4.2 μM, including dose-dependent induction of caspase 3/7 activity, but having little to no effect on the BCL-XL-dependent cells. MIM1’s cytotoxic effect on the MCL-1-dependent cells likewise corresponded to dose-dependent dissociation of the inhibitory MCL-1/BAK complex, as assessed by co-immunoprecipitation analysis. |
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Animal models |
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Dosage form |
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Applications |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Cohen N A, Stewart M L, Gavathiotis E, et al. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chemistry & biology, 2012, 19(9): 1175-1186. | |
| Cas No. | 509102-00-5 | SDF | |
| 别名 | 4-[[[2-(环己基亚氨基)-4-甲基-3(2H)-噻唑基]亚氨基]甲基]-1,2,3-苯三醇,Inhibitor of Mcl-1 | ||
| 化学名 | 4-((E)-(((Z)-2-(cyclohexylimino)-4-methylthiazol-3(2H)-yl)imino)methyl)benzene-1,2,3-triol | ||
| Canonical SMILES | OC1=CC=C(/C=N/N2C(C)=CS/C2=N\C3CCCCC3)C(O)=C1O | ||
| 分子式 | C17H21N3O3S | 分子量 | 347.43 |
| 溶解度 | ≥ 12.15mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| 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 | 2.8783 mL | 14.3914 mL | 28.7828 mL |
| 5 mM | 0.5757 mL | 2.8783 mL | 5.7566 mL |
| 10 mM | 0.2878 mL | 1.4391 mL | 2.8783 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet