| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| ln Vitro |
Regardless of the cells' p53 status, MA242 (0.05-5 μM; 72 hours) strongly suppressed the proliferation of pancreatic cancer cells, with an IC50 ranging from 0.1 to 0.4 μM. Nonetheless, MA242 exhibits minimal impact on the proliferation of normal HPDE cells (IC50=5.81 μM), suggesting that MA242 targets cancer cells specifically [1]. At modest doses, MA242 (0.1-0.5 μM; 24 hours) dramatically lowers the levels of MDM2 and NFAT1 protein in all three cell lines [1]. Regardless of the p53 status, MA242 inhibits cell growth and triggers apoptosis in pancreatic cancer cell lines [1]. Without causing any host damage, MA242 either by itself or in conjunction with gemcitabine can stop pancreatic tumor development and metastasis [1]. In vitro, MA242 inhibits the NFAT1-MDM2 pathway, which causes cytotoxicity against hepatocellular carcinoma (HCC) cells without the need for p53. Selective cytotoxicity against HCC cells is demonstrated by MA242, whose IC50 values range from 0.1-0.31 μM[2].
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| ln Vivo |
Independent of p53, MA242 (IP; 2.5, 5, 10 mg/kg) suppresses the formation of orthotopic pancreatic tumors in vivo [1]. In all models, host toxicity was not observed at these efficacious dosages, and there was no discernible difference in mean body weight between mice treated with MA242 and those not [1].
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| Cell Assay |
Cell viability assay [1]
Cell Types: human pancreatic cancer HPAC, Panc-1, AsPC-1, Mia-Paca-2 and BxPC-3 cell lines; human pancreatic ductal epithelial (HPDE) cell line Tested Concentrations: 0.05, 0.5 and 5 μM Incubation Duration: 72 hrs (hours) Experimental Results: The IC50 of Panc-1, Mia-Paca were 0.14, 0.14, 0.15, 0.25, 0.40 and 5.81 μM -2, AsPC-1, BxPC-3, HPAC and HPDE cells respectively. Western Blot Analysis[1] Cell Types: Human pancreatic cancer HPAC, Panc-1 and AsPC-1 cell lines Tested Concentrations: 0, 0.1, 0.2 and 0.5 μM Incubation Duration: 24 hrs (hours) Experimental Results: MDM2 and NFAT1 expression diminished. |
| Animal Protocol |
Animal/Disease Models: Female 4-6 week old athymic nude mice bearing AsPC-1-Luc or Panc-1-Luc tumors (nu/nu, 4-6 weeks) [1]
Doses: Panc 2.5 or 5 mg/kg - 1 tumor-bearing mouse; AsPC-1 tumor-bearing mice 10 mg/kg Route of Administration: IP; Panc-1 tumor-bearing mice 2.5 or 5 mg/kg/d, 5 days per week for five weeks; Knowledge Property Rights; For AsPC-1 tumor-bearing mice, 10 mg/kg/d, 5 d/wk, for three weeks. Experimental Results: Tumor growth in nude mice bearing Panc-1 orthotopic tumors produced 56.1% and 82.5%, respectively. inhibition. Compared with tumors from control animals, the growth of AsPC-1 orthotopic tumors was Dramatically inhibited by 89.5% (P < 0.01). In both models, tumors in MD242-treated mice demonstrated near-complete regression. |
| References |
[1]. Wang W, et al. Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for Pancreatic Cancer Therapy. Cancer Res. 2018 Oct 1;78(19):5656-5667.
[2]. Wei Wang, et al. MDM2-NFAT1 dual inhibitor, MA242: Effective against hepatocellular carcinoma, independent of p53. Cancer Lett. 2019 Sep 10;459:156-167. |
| Molecular Formula |
C26H21CLF3N3O5S
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|---|---|
| Molecular Weight |
579.9753
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| CAS # |
1049704-18-8
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| Related CAS # |
MA242 free base;1049704-17-7
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N([H])C1=C([H])C2C3=C(C1=O)N(C([H])=C3C([H])([H])C([H])([H])N=2)S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(=O)=O.FC(C(=O)O[H])(F)F
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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 | 1.7242 mL | 8.6210 mL | 17.2420 mL | |
| 5 mM | 0.3448 mL | 1.7242 mL | 3.4484 mL | |
| 10 mM | 0.1724 mL | 0.8621 mL | 1.7242 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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