Size | Price | Stock | Qty |
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1mg |
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5mg |
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10mg |
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Other Sizes |
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Targets |
Hdm2[1]; Apoptosis[1]; Antimalarial[2]
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ln Vitro |
Tumor cells expressing wild-type p53 are specifically eliminated by HLI373 (3-15 μM; 15 hours)[1]. Cellular Hdm2 is stabilized by HLI373 (10–50 μM) in a dose-dependent way. HLI373 (3 μM) stimulates transcription of p53[1].HLI373 inhibits Hdm2's auto-ubiquitylation with selectivity[1]. P53 is degraded by co-transfection with plasmids encoding Hdm2 and p53. Degradation of p53 is prevented by incubating with HLI373 (5–10 μM) for 8 hours. In cells, HLI373 raises the levels of the proteins p53 and Hdm2[1]. HLI 373 demonstrates early growth inhibition and reduced IC50 values (below 6 μM) against the chloroquine-sensitive P. falciparum D6 strain (PfD6) as well as the chloroquine-resistant P. falciparum W2 strain (PfW2)[2]. The MDM2 inhibitor HLI-373 can stop the activity of its substrate protein p53 being ubiquitinated by blocking the activity of ubiquitin E3 ligase. As an E3 ubiquitin ligase, HLI-373 targets the C-terminus[3].
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Cell Assay |
Cell Viability Assay[1]
Cell Types: Wild type p53 mouse embryo fibroblasts (MEFs), and p53-deficient MEFs Tested Concentrations: 3, 10, 15 μM Incubation Duration: 15 hrs (hours) Experimental Results: Increased cell death in wild type p53 MEFs in a dose-dependent manner, p53-deficient MEFs were relatively resistant. Western Blot Analysis[1] Cell Types: U2OS cells Tested Concentrations: 5, 10 μM Incubation Duration: 8 hrs (hours) Experimental Results: Blocked p53 degradation caused by co-transfection with plasmids encoding p53 and Hdm2. |
References |
[1]. Jirouta Kitagaki, et al. Targeting Tumor Cells Expressing p53 With a Water-Soluble Inhibitor of Hdm2. Mol Cancer Ther. 2008 Aug;7(8):2445-54.
[2]. Jagrati Jain, et al. Inhibitors of Ubiquitin E3 Ligase as Potential New Antimalarial Drug Leads. BMC Pharmacol Toxicol. 2017 Jun 2;18(1):40. [3]. Ying Chen, et al. MDM2 Promotes Epithelial-Mesenchymal Transition and Metastasis of Ovarian Cancer SKOV3 Cells. Br J Cancer. 2017 Oct 10;117(8):1192-1201. |
Molecular Formula |
C18H25CL2N5O2
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Molecular Weight |
414.33
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CAS # |
1782531-99-0
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Related CAS # |
1782531-99-0(HCl);502137-98-6;
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C1C2/C(/C3C=CC=CC=3N(C)C=2NC(N1C)=O)=N/CCCN(C)C
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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: Please store this product in a sealed and protected environment, 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)
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Solubility (In Vitro) |
H2O : ~38 mg/mL (~91.71 mM)
DMSO : ~4 mg/mL (~9.65 mM) |
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4135 mL | 12.0677 mL | 24.1354 mL | |
5 mM | 0.4827 mL | 2.4135 mL | 4.8271 mL | |
10 mM | 0.2414 mL | 1.2068 mL | 2.4135 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.