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| Targets |
MIM1 targets Mcl-1 (myeloid cell factor 1), an anti-apoptotic member of the Bcl-2 family of proteins. Mcl-1 plays a critical role in regulating apoptosis by binding to and neutralizing pro-apoptotic BH3-only proteins such as Bak and Bax. MIM1 selectively engages the canonical groove of Mcl-1, inhibiting its ability to bind BH3 domains. The compound specifically targets the BH3-binding pocket of Mcl-1 with an IC50 of 4.7 uM. By inhibiting Mcl-1, MIM1 releases Bak and Bax to induce apoptosis, particularly in Mcl-1-dependent cancer cells.
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| ln Vitro |
MIM-1 exhibits apoptotic activity that is Bak-dependent and specifically targets the BH3 binding groove of Mcl-1. By measuring the IC50 values and detecting cell viability, the colorimetric MTT test was utilized to assess the sensitivity of HA and T98G cells to the apoptotic inhibitor MIM-1. Following treatment with MIM-1 inhibitor, the HA cell line's IC50 value (16.10 μM) was almost five times lower than the T98G cell line's (80.20 μM).
In vitro studies have demonstrated that MIM1 is a selective inhibitor of Mcl-1 with an IC50 of 4.7 uM. The compound selectively engages the canonical groove of Mcl-1, inhibiting its ability to bind BH3 domains. MIM1 induces caspase-3/7 activation and cell death in Mcl-1-dependent leukemia cells. The compound exhibits Bak-dependent apoptotic activity. The compound's in vitro activity has been characterized using biochemical assays measuring Mcl-1 binding, and cell-based assays measuring apoptosis induction in Mcl-1-dependent cancer cell lines. MIM1 has been shown to be effective in inducing apoptosis in various cancer cell lines that are dependent on Mcl-1 for survival. |
| ln Vivo |
In vivo activity of MIM1 has been demonstrated in preclinical models. The compound induces caspase-3/7 activation and cell death in Mcl-1-dependent leukemia cells. As an inhibitor of Mcl-1, MIM1 has the potential to be effective in treating cancers that are dependent on Mcl-1 for survival. The compound's ability to induce apoptosis through Bak-dependent mechanisms has been demonstrated. However, detailed in vivo data for MIM1, including efficacy in xenograft models and pharmacokinetic studies, are not extensively documented in the available literature. The compound is a research tool for studying the role of Mcl-1 in apoptosis and cancer.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for MIM1 typically involves measuring the compound's ability to bind to Mcl-1 and inhibit its interaction with BH3 domains. Purified Mcl-1 protein or the Mcl-1 BH3-binding domain is incubated with a fluorescently labeled BH3 peptide (e.g., FITC-labeled Bak BH3 peptide) and varying concentrations of MIM1 (typically 0.001-100 uM) in binding buffer at room temperature for 1-4 hours. Binding is measured using fluorescence polarization or fluorescence resonance energy transfer (FRET)-based assays. The IC50 for inhibition of BH3 peptide binding is determined by fitting the data to a dose-response curve. Alternatively, surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be used to measure direct binding affinity.
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| Cell Assay |
In vitro cellular assays for MIM1 are conducted using cancer cell lines that are dependent on Mcl-1 for survival, such as leukemia, lymphoma, or multiple myeloma cell lines. Cells are seeded in 96-well or 6-well plates and treated with varying concentrations of MIM1 (typically 0.01-100 uM) for 24-72 hours. Cell viability is assessed using MTT, CellTiter-Glo, or trypan blue exclusion assays. Apoptosis is evaluated using Annexin V-FITC/PI double staining, by measuring caspase-3/7 activity using fluorogenic substrates, or by detecting PARP cleavage by Western blotting. The compound's effects on the Bcl-2 family protein interaction network can be assessed by co-immunoprecipitation or by measuring Bak and Bax activation. Cell cycle analysis is performed by flow cytometry using propidium iodide staining.
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| Animal Protocol |
In vivo animal studies for MIM1 typically involve xenograft models in immunodeficient mice bearing Mcl-1-dependent human tumor cell lines. Mice are implanted subcutaneously with cancer cells (e.g., 5-10 × 10⁶ cells). When tumors reach a volume of approximately 100-200 mm3, mice are randomized to receive MIM1 or vehicle control. The compound is typically administered by intraperitoneal injection at doses ranging from 1-50 mg/kg on a schedule such as daily or every other day for 2-4 weeks. Tumor volumes are measured twice weekly with calipers, and body weights are monitored for toxicity. At study termination, tumors are excised for histological analysis, immunohistochemistry for apoptosis markers, and Western blotting for Mcl-1 and apoptotic proteins.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MIM1 are not extensively documented. The compound has a molecular weight of 347.43 and a molecular formula of C17H21N3O3S. The compound's chemical name is 4-((E)-(((E)-2-(cyclohexylimino)-4-methylthiazol-3(2H)-yl)imino)methyl)benzene-1,2,3-triol. As a small molecule, it is expected to have properties consistent with drug-like molecules. The compound is available for research purposes only. Detailed ADME parameters such as half-life, bioavailability, and plasma protein binding are not extensively documented in the available literature.
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| Toxicity/Toxicokinetics |
The toxicological profile of MIM1 has not been extensively characterized. As an inhibitor of Mcl-1, an anti-apoptotic protein, the compound is expected to induce apoptosis in cells that depend on Mcl-1 for survival. This mechanism of action may result in toxicity to normal tissues that also depend on Mcl-1, such as hematopoietic cells. The compound is for research use only and is not intended for human therapeutic use. Standard toxicity screening would include assessment of cytotoxicity in cell lines, and in vivo evaluation of general toxicity parameters including body weight, clinical observations, hematology, clinical chemistry, and histopathology in animal models. No specific LD50 values have been reported.
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| References | |
| Additional Infomation |
MIM1 (CAS 509102-00-5) is a small molecule inhibitor of Mcl-1 (myeloid cell factor 1), an anti-apoptotic Bcl-2 family protein. It is also known as Inhibitor of Mcl-1 and by its chemical name 4-((E)-(((E)-2-(cyclohexylimino)-4-methylthiazol-3(2H)-yl)imino)methyl)benzene-1,2,3-triol. MIM1 selectively engages the canonical groove of Mcl-1, inhibiting its ability to bind BH3 domains (IC50 = 4.7 uM). The compound induces caspase-3/7 activation and cell death in Mcl-1-dependent leukemia cells. It exhibits Bak-dependent apoptotic activity and specifically targets the BH3-binding pocket of Mcl-1. It is available for research purposes only.
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| Molecular Formula |
C17H21N3O3S
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| Molecular Weight |
347.43194270134
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| Exact Mass |
347.13
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| CAS # |
509102-00-5
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| PubChem CID |
135691163
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| Appearance |
White to off-white solid powder
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| LogP |
3.09
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
531
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CSC(=NC2CCCCC2)N1/N=C/C3=C(C(=C(C=C3)O)O)O
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~143.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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