| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 250mg | |||
| Other Sizes |
| Targets |
MI-1061 targets the MDM2 protein (mouse double minute 2 homolog), which is a negative regulator of the tumor suppressor p53. MDM2 binds to the N-terminal transactivation domain of p53, inhibiting its transcriptional activity and promoting its ubiquitination and proteasomal degradation. By inhibiting the MDM2-p53 interaction with an IC50 of 4.4 nM and a Ki of 0.16 nM, MI-1061 prevents MDM2-mediated p53 degradation, allowing p53 to accumulate and activate the transcription of pro-apoptotic and cell cycle arrest genes. The compound's chemical stability and oral bioavailability make it a valuable tool for studying the p53 pathway in cancer research.
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| ln Vitro |
The IC50 of MI-1061 in the p53 knockout cell line HCT-116 p53–/– cell line is >10000 nM, while the IC50 in the SJSA-1 and HCT-116 p53+/+ cell lines is 100 and 250 nM, respectively [1].
MI-1061 demonstrates potent in vitro activity as an MDM2 inhibitor. The compound inhibits the MDM2-p53 interaction with an IC50 of 4.4 nM and a Ki of 0.16 nM. Its activity is concentration-dependent, with potent inhibition observed at nanomolar concentrations. MI-1061 activates p53 in cell-based assays, leading to the induction of p53 target genes and apoptosis. The compound is chemically stable, making it suitable for various in vitro applications. MI-1061 has been shown to cause apoptosis in SJSA-1 xenograft tumor tissues. Its potency and selectivity for MDM2 make it a valuable tool for studying p53-mediated tumor suppression and evaluating MDM2 inhibition as a therapeutic strategy for cancer. |
| ln Vivo |
The mouse SJSA-1 xenograft tumor model can experience tumor regression with MI-1061 (100 mg/kg; exo once daily for 14 days) [1].
In vivo, MI-1061 has demonstrated significant antitumor efficacy in mouse xenograft models. The compound is orally bioavailable and activates p53 in tumor tissues. MI-1061 causes apoptosis in SJSA-1 xenograft tumor tissues in mice with antitumor activity. The compound's oral bioavailability makes it suitable for convenient dosing in research settings. Comprehensive in vivo efficacy studies have been reported in research publications. MI-1061 has been evaluated in SJSA-1 xenograft model mice. Its ability to activate p53 and induce apoptosis in tumor tissues supports its potential for cancer research. The compound's chemical stability contributes to its favorable in vivo properties. |
| Enzyme Assay |
In vitro binding assays for MI-1061 involve measuring the inhibition of the MDM2-p53 interaction. Recombinant MDM2 protein is incubated with a fluorescently labeled or radiolabeled p53 peptide and varying concentrations of the test compound. The displacement of the labeled peptide is measured using fluorescence polarization, AlphaScreen, or scintillation proximity assays. IC50 values are calculated from competition curves using non-linear regression analysis. The compound has an IC50 of 4.4 nM and a Ki of 0.16 nM. Selectivity assays compare the compound's activity against other protein-protein interactions. Each concentration is typically tested in duplicate or triplicate with appropriate positive controls (known MDM2 inhibitors) and vehicle controls.
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| Cell Assay |
In vitro cellular assays for MI-1061 are performed using cancer cell lines with wild-type p53, such as SJSA-1 osteosarcoma cells. Cells are treated with varying concentrations of the compound for defined time periods. p53 activation is assessed by measuring p53 protein levels by Western blot. p53 target gene expression (p21, MDM2, PUMA, Bax) is measured by qRT-PCR. Cell proliferation and viability are measured using MTT or CellTiter-Glo assays. Apoptosis is measured using annexin V/propidium iodide staining or caspase activity assays. Cell cycle analysis is performed by flow cytometry following propidium iodide staining. Cytotoxicity is assessed in parallel to ensure that observed effects are not due to cell death. IC50 values for inhibition of cell proliferation are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: SCID (severe combined immunodeficient) mouse carrying SJSA-1 osteosarcoma xenografts [1]
Doses: 100 mg/kg Route of Administration: Po; one time/day for 14 days Experimental Results: Demonstrated potent anti-tumor activity and achieved significant of tumor regression. In vivo animal studies for MI-1061 are conducted using mouse xenograft models of cancer, particularly SJSA-1 osteosarcoma xenografts. Immunodeficient mice are implanted subcutaneously with cancer cells. Once tumors reach a predetermined size, animals are randomized into treatment groups and administered MI-1061 via oral gavage at various doses and schedules. Tumor growth is measured using calipers. p53 activation and apoptosis are assessed in tumor tissues by immunohistochemistry or Western blot. Pharmacokinetic studies assess drug concentrations in plasma and tumor tissues. Animals are monitored for clinical signs and body weight. Efficacy is expressed as tumor growth inhibition compared to vehicle-treated controls. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of MI-1061 have been characterized in preclinical studies. The compound has a molecular formula of C30H26Cl2FN3O4 and a molecular weight of 582.45 g/mol. Its chemical name is 4-((3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indoline]-5'-carboxamido)benzoic acid. MI-1061 is orally bioavailable. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized in animal models. The compound's chemical stability contributes to its favorable pharmacokinetic properties. Its pharmacokinetic profile supports its use in preclinical studies of cancer.
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| Toxicity/Toxicokinetics |
MI-1061 is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As an MDM2 inhibitor that activates p53, the compound would be expected to have effects on cell cycle regulation and apoptosis. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
MI-1061 is a novel chemically stable, potent, and efficacious MDM2 inhibitor. It inhibits the MDM2-p53 interaction with an IC50 of 4.4 nM and a Ki of 0.16 nM. MI-1061 is orally bioavailable and activates p53, causing apoptosis in SJSA-1 xenograft tumor tissues in mice with antitumor activity. The compound has a molecular formula of C30H26Cl2FN3O4 and a molecular weight of 582.45 g/mol. MI-1061 has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only.
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| Molecular Formula |
C30H26CL2FN3O4
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|---|---|
| Molecular Weight |
582.449549198151
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| Exact Mass |
581.128
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| CAS # |
1410737-34-6
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| Related CAS # |
MI-1061 TFA;1410737-35-7
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| PubChem CID |
70677271
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
40
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
3
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| SMILES |
ClC1C=CC2=C(C=1)NC([C@@]12[C@@H](C2C=CC=C(C=2F)Cl)[C@H](C(NC2C=CC(C(=O)O)=CC=2)=O)NC21CCCCC2)=O
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| InChi Key |
BIDSEXPFIMKDMF-LOLKONATSA-N
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| InChi Code |
InChI=1S/C30H26Cl2FN3O4/c31-17-9-12-20-22(15-17)35-28(40)30(20)23(19-5-4-6-21(32)24(19)33)25(36-29(30)13-2-1-3-14-29)26(37)34-18-10-7-16(8-11-18)27(38)39/h4-12,15,23,25,36H,1-3,13-14H2,(H,34,37)(H,35,40)(H,38,39)/t23-,25+,30+/m0/s1
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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 |
| 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 : ~160 mg/mL (~274.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4 mg/mL (6.87 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 40.0 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: 4 mg/mL (6.87 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 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. View More
Solubility in Formulation 3: ≥ 4 mg/mL (6.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7169 mL | 8.5844 mL | 17.1689 mL | |
| 5 mM | 0.3434 mL | 1.7169 mL | 3.4338 mL | |
| 10 mM | 0.1717 mL | 0.8584 mL | 1.7169 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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