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100mg | ||
250mg | ||
500mg |
ln Vitro |
Tumor cells expressing wild-type p53 are specifically eliminated by HLI373 (3-15 μM; 15 hours) [1]. Cellular Hdm2 is stabilized in a dose-dependent manner by HLI373 (10-50 μM). Transcription of p53 is activated by HLI373 (3 μM) [1]. HLI373 specifically prevents Hdm2 from being autoubiquitinated [1]. Degradation of p53 occurs when plasmids encoding Hdm2 and p53 are cotransfected. HLI373 (5–10 μM; 8 hours) incubation stops p53 degradation. HLI373 raises the amounts of the proteins Hdm2 and p53 in cells [1]. In addition, HLI 373 demonstrated early growth inhibition and low IC50 values (less than 6 μM) against the chloroquine-sensitive P. falciparum D6 strain (PfD6) and the chloroquine-resistant P. falciparum W2 strain (PfW2) [2]. The MDM2 inhibitor HLI-373 prevents the substrate protein p53 from being ubiquitinated by blocking its ubiquitin E3 ligase function. HLI-373 functions as an E3 ubiquitin ligase and targets the C terminus [3].
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Cell Assay |
Cell Viability Assay[1]
Cell Types: Wild-type p53 mouse embryonic fibroblasts (MEFs) and p53-deficient MEFs Tested Concentrations: 3, 10, 15 μM Incubation Duration: 15 hrs (hours) Experimental Results: Cell death of wild-type p53 MEFs at dose In a dependent manner, p53-deficient MEFs were relatively resistant. Western Blot Analysis[1] Cell Types: U2OS Cell Tested Concentrations: 5, 10 μM Incubation Duration: 8 hrs (hours) Experimental Results: Blocks p53 degradation caused by co-transfection of 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 |
C18H23N5O2
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Molecular Weight |
341.415
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Exact Mass |
341.1852
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CAS # |
502137-98-6
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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(/C3=C([H])C([H])=C([H])C([H])=C3N(C([H])([H])[H])C=2N([H])C(N1C([H])([H])[H])=O)=N/C([H])([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H]
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Synonyms |
HLI 373; HLI-373; HLI373
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.9289 mL | 14.6447 mL | 29.2894 mL | |
5 mM | 0.5858 mL | 2.9289 mL | 5.8579 mL | |
10 mM | 0.2929 mL | 1.4645 mL | 2.9289 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.