| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
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| 25mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
MDM2 (Ki = 0.88 nM); MDM2 (Kd = 8.2 nM)
MI-773 targets the MDM2-p53 interaction. MDM2 is a negative regulator of the tumor suppressor p53. By binding to MDM2 with high affinity (Ki=0.88 nM, Kd=8.2 nM), MI-773 blocks the MDM2-p53 interaction. This prevents the degradation of p53, leading to the activation of p53-mediated tumor suppressor pathways, including cell cycle arrest and apoptosis. |
|---|---|
| ln Vitro |
MI-773 binds to MDM2 with a Ki of 0.88 nM. MI-773 potently inhibits cell growth in cancer cell lines, including SJSA-1 (IC50, 0.092 μM), RS4;11 (IC50, 0.089 μM), LNCaP (IC50, 0.27 μM), and HCT-116 (IC50, 0.20 μM) cells, and displays high selectivity over cancer cell lines with mutated or deleted p53, including SAOS-2 (IC50, >10 μM), PC-3 (IC50, >10 μM), SW620 (IC50, >10 μM), and HCT-116 (p53-/-) (IC50, >20 μM) cells. [1]
In vitro, MI-773 is a potent inhibitor of the MDM2-p53 interaction. It binds to MDM2 with high affinity (Ki=0.88 nM, Kd=8.2 nM). It has antitumor activity in vitro. Its activity is typically measured using biochemical and cell-based assays. These in vitro studies confirm MI-773's activity as an MDM2-p53 inhibitor. |
| ln Vivo |
MI-773 (p.o.) effectively inhibits tumor growth in a dose-dependent manner in the SJSA-1 osteosarcoma, acute lymphoblastic leukemia RS4;11, LNCaP prostate cancer, and HCT-116 colon cancer xenograft model (10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg). [1]
In vivo, MI-773 has been investigated for the treatment of cancers. It has been studied in a Phase I trial against solid tumors, but the trial has been discontinued. As an MDM2-p53 inhibitor, it has potential applications in cancer therapy. |
| Enzyme Assay |
Using a Fluorescence-polarization (FP) binding assay, the binding affinities of p53 peptide and MDM2 inhibitors to the MDM2 protein are assessed. Using a competitive FP-based assay, MI-773's binding affinities to Bcl-2, Bcl-xL, Mcl-1, and β--catenin are identified, and its affinity to MDMx is identified using Biolayer Interferometry technology.
In vitro biochemical assays for MI-773 measure its binding to MDM2. Binding assays are performed using purified MDM2 protein and a labeled probe. MI-773 is added at increasing concentrations to compete with the labeled probe. The Ki or Kd is determined from binding curves. |
| Cell Assay |
In a water-soluble tetrazolium-based assay, cell growth inhibition activity is assessed. Trypan blue staining is used to measure cell death, and a kit for staining with Annexin V-FLUOS determines apoptosis.
In vitro cell-based assays for MI-773 are used to study its effects on p53 signaling. Cancer cells with wild-type p53 are treated with MI-773, and the expression of p53 target genes is measured by quantitative PCR. Cell proliferation and apoptosis are assessed using standard assays. |
| Animal Protocol |
In vivo animal experiments for MI-773 have been conducted in xenograft models of cancer. In a typical study, immunodeficient mice are implanted with human tumor cells and treated with MI-773. Tumor growth is monitored. The compound's ability to inhibit tumor growth is assessed.
|
| ADME/Pharmacokinetics |
MI-773 has a molecular weight of 562.50 g/mol and a molecular formula of C29H34Cl2FN3O3. It has a CAS number of 1303607-07-9. It is a solid compound. For storage, it is recommended to keep the powder at -20°C. Detailed pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have not been extensively characterized.
|
| Toxicity/Toxicokinetics |
Detailed toxicity data for MI-773 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. MI-773 is an MDM2-p53 inhibitor, and its toxicity would be related to its effects on p53-mediated signaling in normal tissues. As with all research chemicals, standard laboratory safety precautions should be followed.
|
| References | |
| Additional Infomation |
MI-773 is a research compound and is not approved for any clinical or therapeutic use. It is a potent MDM2-p53 protein-protein interaction (PPI) inhibitor. It binds to MDM2 with high affinity (Ki=0.88 nM, Kd=8.2 nM). It has antitumor activity and has been investigated for the treatment of cancers. It has been studied in a Phase I trial against solid tumors, but the trial has been discontinued.
|
| Molecular Formula |
C29H34CL2FN3O3
|
|---|---|
| Molecular Weight |
562.503
|
| Exact Mass |
561.196
|
| Elemental Analysis |
C, 61.92; H, 6.09; Cl, 12.60; F, 3.38; N, 7.47; O, 8.53
|
| CAS # |
1303607-07-9
|
| Related CAS # |
1303607-07-9; 1303607-60-4;
|
| PubChem CID |
52938482
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.16
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
38
|
| Complexity |
895
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
O=C([C@H](N[C@@H]1CC(C)(C)C)[C@H](C2=CC=CC(Cl)=C2F)[C@]31C(NC4=C3C=CC(Cl)=C4)=O)N[C@H]5CC[C@H](O)CC5
|
| InChi Key |
IDKAKZRYYDCJDU-YJRDPZTCSA-N
|
| InChi Code |
InChI=1S/C29H34Cl2FN3O3/c1-28(2,3)14-22-29(19-12-7-15(30)13-21(19)34-27(29)38)23(18-5-4-6-20(31)24(18)32)25(35-22)26(37)33-16-8-10-17(36)11-9-16/h4-7,12-13,16-17,22-23,25,35-36H,8-11,14H2,1-3H3,(H,33,37)(H,34,38)/t16?,17?,22-,23+,25-,29+/m1/s1
|
| Chemical Name |
(2'R,3S,3'S,5'R)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-N-(4-hydroxycyclohexyl)-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carboxamide
|
| Synonyms |
MI 773; MI773; MI-773
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~177.8 mM)
Ethanol: ~31 mg/mL (~55.1 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.44 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 25.0 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: ≥ 2.5 mg/mL (4.44 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), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.44 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 | 1.7778 mL | 8.8889 mL | 17.7778 mL | |
| 5 mM | 0.3556 mL | 1.7778 mL | 3.5556 mL | |
| 10 mM | 0.1778 mL | 0.8889 mL | 1.7778 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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