YH239-EEp53-MDM2 antagonist, potent CAS# 1364488-67-4 |
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Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 1364488-67-4 | SDF | Download SDF |
| PubChem ID | 56943013 | Appearance | Powder |
| Formula | C25H27Cl2N3O4 | M.Wt | 504.41 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 55 mg/mL (109.04 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | ethyl 3-[2-(tert-butylamino)-1-[(4-chlorophenyl)methyl-formylamino]-2-oxoethyl]-6-chloro-1H-indole-2-carboxylate | ||
| SMILES | CCOC(=O)C1=C(C2=C(N1)C=C(C=C2)Cl)C(C(=O)NC(C)(C)C)N(CC3=CC=C(C=C3)Cl)C=O | ||
| Standard InChIKey | OTUBDDRFPQLPKD-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C25H27Cl2N3O4/c1-5-34-24(33)21-20(18-11-10-17(27)12-19(18)28-21)22(23(32)29-25(2,3)4)30(14-31)13-15-6-8-16(26)9-7-15/h6-12,14,22,28H,5,13H2,1-4H3,(H,29,32) | ||
| 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 | YH239-EE is a potent antagonist of p53-MDM2 and an inducer of apoptosis. | |||||
| Targets | p53-MDM2 | |||||
YH239-EE Dilution Calculator
YH239-EE Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9825 mL | 9.9126 mL | 19.8251 mL | 39.6503 mL | 49.5629 mL |
| 5 mM | 0.3965 mL | 1.9825 mL | 3.965 mL | 7.9301 mL | 9.9126 mL |
| 10 mM | 0.1983 mL | 0.9913 mL | 1.9825 mL | 3.965 mL | 4.9563 mL |
| 50 mM | 0.0397 mL | 0.1983 mL | 0.3965 mL | 0.793 mL | 0.9913 mL |
| 100 mM | 0.0198 mL | 0.0991 mL | 0.1983 mL | 0.3965 mL | 0.4956 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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YH239-EE is a potent antagonist of p53-MDM2 [1].
p53 is a transcription factor and functions as a tumor suppressor. MDM2 is a negative regulator of p53. The interaction of p53 and MDM2 has emerged as a novel target for anticancer drugs [1].
YH239-EE is a potent p53-MDM2 antagonist. In OCI-AML-3 cells, YH239-EE potently inhibited cell proliferation. In AML cell lines, YH239-EE induced a cell cycle arrest and cell accumulation in the sub-G1 phase. YH239-EE induced apoptosis by 11.8-fold, 5.6-fold and 13.1-fold in OCI-AML-3, MOLM-13 and NB4 AML cell lines, respectively. In MOLM-13 cells, YH239 exhibited almost no apoptotic effect. However, YH239-EE significantly induced apoptosis. In MOLM-13 cells, (+)-YH239-EE and (−)-YH239-EE inhibited metabolic activity with EC50 values of 7.5 μM and 25.2 μM and induced apoptosis with 13.7% and 51.5% viable cells, respectively. (+)-YH239-EE (20 μM) induced p53 and significantly activated caspase 3 and 7 [1].
Reference:
[1]. Huang Y, Wolf S, Beck B, et al. Discovery of highly potent p53-MDM2 antagonists and structural basis for anti-acute myeloid leukemia activities. ACS Chem Biol, 2014, 9(3): 802-811.
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Discovery of highly potent p53-MDM2 antagonists and structural basis for anti-acute myeloid leukemia activities.[Pubmed:24405416]
ACS Chem Biol. 2014 Mar 21;9(3):802-11.
The inhibition of p53-MDM2 interaction is a promising new approach to non-genotoxic cancer treatment. A potential application for drugs blocking the p53-MDM2 interaction is acute myeloid leukemia (AML) due to the occurrence of wild type p53 (wt p53) in the majority of patients. Although there are very promising preclinical results of several p53-MDM2 antagonists in early development, none of the compounds have yet proven the utility as a next generation anticancer agent. Herein we report the design, synthesis and optimization of YH239-EE (ethyl ester of the free carboxylic acid compound YH239), a potent p53-MDM2 antagonizing and apoptosis-inducing agent characterized by a number of leukemia cell lines as well as patient-derived AML blast samples. The structural basis of the interaction between MDM2 (the p53 receptor) and YH239 is elucidated by a co-crystal structure. YH239-EE acts as a prodrug and is the most potent compound that induces apoptosis in AML cells and patient samples. The observed superior activity compared to reference compounds provides the preclinical basis for further investigation and progression of YH239-EE.
