MI-773MDM2 inhibitor CAS# 1303607-07-9 |
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Quality Control & MSDS
3D structure
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Number of papers citing our products
| Cas No. | 1303607-07-9 | SDF | Download SDF |
| PubChem ID | 52938482 | Appearance | Powder |
| Formula | C29H34Cl2FN3O3 | M.Wt | 562.5 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 53 mg/mL (94.22 mM) *"≥" means soluble, but saturation unknown. | ||
| 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 | ||
| SMILES | CC(C)(C)CC1C2(C(C(N1)C(=O)NC3CCC(CC3)O)C4=C(C(=CC=C4)Cl)F)C5=C(C=C(C=C5)Cl)NC2=O | ||
| Standard InChIKey | IDKAKZRYYDCJDU-YJRDPZTCSA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | MI-773 is a new small molecule inhibitor of the MDM2-p53 interaction, binds to MDM2 with high affinity (Ki=0.88 nM) and blocks the p53-MDM2 interaction.In Vitro:MI-773 potently induces expression of p53 and its downstream targets p21, MDM2, and induces phosphorylation of p53 (serine 392) in low passage primary human ACC cells. Notably, MI-773 induces a dose-dependent increase in the fraction of apoptotic ACC cells and in the fraction of cells in the G1 phase of cell cycle (P<0.05). Consequently, MI-773 causes apoptotic cell death[1]. MI-773 is an advanced synthetic small molecule inhibitor, displays high binding affinity against MDM2 (Kd=8.2 nM)[2].In Vivo:MI-773 at 10 mg/kg modestly reduces the rate of tumor growth, whereas 100 mg/kg causes significant tumor regression. Control tumors reach an average of 1,000 mm3 at 20 days of treatment, compare to an average volume of 600 mm3 for the 10 mg/kg group and 30 mm3 for the 100 mg/kg group. Kaplan-Meier analysis shows an increase in tumor failure, define as two times increase in tumor volume as compared to pretreatment volume (P=0.044), for vehicle-treated mice when compare to mice treated with 100 mg/kg MI-773[1]. References: | |||||
MI-773 Dilution Calculator
MI-773 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.7778 mL | 8.8889 mL | 17.7778 mL | 35.5556 mL | 44.4444 mL |
| 5 mM | 0.3556 mL | 1.7778 mL | 3.5556 mL | 7.1111 mL | 8.8889 mL |
| 10 mM | 0.1778 mL | 0.8889 mL | 1.7778 mL | 3.5556 mL | 4.4444 mL |
| 50 mM | 0.0356 mL | 0.1778 mL | 0.3556 mL | 0.7111 mL | 0.8889 mL |
| 100 mM | 0.0178 mL | 0.0889 mL | 0.1778 mL | 0.3556 mL | 0.4444 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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MI-773 is a small molecule inhibitor of MDM2 with IC50 value of 62nM [1].
MI-773 is a small molecule MDM2 antagonist. It is a spirooxindole derivative. MI-773 shows a high MDM2 affinity with IC50 value of 62nM in the FP competitive binding experiment. In the in vitro cell-based assay, MI-773 shows a similar inhibition efficacy with its enantiomer MI-77301. The GI50 values are 58nM and 33nM for MI-773 and MI-77301, respectively. Both MI-773 and MI-77301 exert considerable activity at dose of 100 mg/kg in mouse xenograft models of osteosarcoma, prostate cancer, colorectal cancer, leukemia or melanoma. Currently, an international and multicenter phase I trial of MI-773 is underway for patients with liposarcomas and other p53-wild-type tumors [1, 2].
References:
[1] Zak K, Pecak A, Rys B, Wladyka B, Dömling A, Weber L, Holak TA, Dubin G. Mdm2 and MdmX inhibitors for the treatment of cancer: a patent review (2011-present). Expert Opin Ther Pat. 2013 Apr;23(4):425-48.
[2] Shoushtari AN, Van Tine BA, Schwartz GK. Novel treatment targets in sarcoma: more than just the GIST. Am Soc Clin Oncol Educ Book. 2014:e488-95.
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Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma.[Pubmed:27764791]
Oncotarget. 2016 Dec 13;7(50):82757-82769.
Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common childhood extracranial malignant tumor. In NB, somatic mutations of the tumor suppressor, p53, are exceedingly rare. Unlike in adult tumors, the majority of p53 downstream functions are still intact in NB cells with wild-type p53. Thus, restoring p53 function by blocking its interaction with p53 suppressors such as MDM2 is a viable therapeutic strategy for NB treatment. Herein, we show that MDM2 inhibitor SAR405838 is a potent therapeutic drug for NB. SAR405838 caused significantly decreased cell viability of p53 wild-type NB cells and induced p53-mediated apoptosis, as well as augmenting the cytotoxic effects of doxorubicin (Dox). In an in vivo orthotopic NB mouse model, SAR405838 induced apoptosis in NB tumor cells. In summary, our data strongly suggest that MDM2-specific inhibitors like SAR405838 may serve not only as a stand-alone therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact MDM2-p53 axis.
