Physicochemical Properties
| Molecular Formula | C24H20CLN3O3S |
| Molecular Weight | 465.95 |
| Exact Mass | 465.091 |
| CAS # | 1049704-17-7 |
| Related CAS # | MA242;1049704-18-8 |
| PubChem CID | 70878625 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 4.4 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 896 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | OAGZTFIEDOSHHS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H20ClN3O3S/c1-15-2-8-19(9-3-15)32(30,31)28-14-17-10-11-26-20-12-21(24(29)23(28)22(17)20)27-13-16-4-6-18(25)7-5-16/h2-9,12,14,27H,10-11,13H2,1H3 |
| Chemical Name | 10-[(4-chlorophenyl)methylamino]-2-(4-methylphenyl)sulfonyl-2,7-diazatricyclo[6.3.1.04,12]dodeca-1(12),3,7,9-tetraen-11-one |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | MDM2, NFAT1[1] |
| ln Vitro | Regardless of the cells' p53 status, MA242 (0.05-5 μM; 72 hours) free base substantially suppresses the proliferation of pancreatic cancer cells, with IC50s ranging from 0.1 to 0.4 μM. On the other hand, the proliferation of normal HPDE cells is minimally affected by MA242 free base (IC50=5.81 μM), suggesting that MA242 selectively affects cancer cells[1]. In all three cell lines, MA242 (0.1-0.5 μM; 24 hours) free base dramatically reduces the MDM2 and NFAT1 protein levels at low concentrations[1]. Regardless of the p53 status, MA242 free base reduces cell growth and promotes apoptosis in pancreatic cancer cell lines[1]. Without causing any host toxicity, pancreatic tumor development and metastasis are inhibited by MA242 free base either by itself or in conjunction with gemcitabine[1]. In vitro, the NFAT1-MDM2 pathway is inhibited by the free base MA242, which exhibits cytotoxicity against hepatocellular carcinoma (HCC) cells without the need for p53. MA242 exhibited specific cytotoxicity towards HCC cells, as evidenced by its IC50 values, which ranged from 0.1-0.31 μM[2]. |
| ln Vivo | Independent of p53, MA242 (IP; 2.5, 5, 10 mg/kg) free base inhibits the formation of orthotopic pancreatic tumors in vivo[1]. In both scenarios, the average body weights of the mice treated with vehicle and MA242 free base did not differ significantly, and at these efficacious levels, there was no discernible host toxicity[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: The human pancreatic cancer HPAC, Panc-1, AsPC-1, Mia-Paca-2 and BxPC -3 cell lines; The human pancreatic ductal epithelium (HPDE) cell line Tested Concentrations: 0.05, 0.5, and 5 μM Incubation Duration: 72 hrs (hours) Experimental Results: The IC50s are 0.14, 0.14, 0.15, 0.25, 0.40, and 5.81 μM for Panc- 1, Mia-Paca-2, AsPC-1, BxPC-3, HPAC, and HPDE cells, respectively. Western Blot Analysis[1] Cell Types: The 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: diminished the expression of MDM2 and NFAT1. |
| Animal Protocol |
Animal/Disease Models: Female 4-6weeks old athymic nude mice (nu/nu, 4-6 weeks) bearing AsPC-1-Luc or Panc-1-Luc tumor[1] Doses: 2.5 or 5 mg/kg for Panc-1 tumor-bearing mice; 10 mg/kg for AsPC-1 tumor-bearing mice Route of Administration: IP; 2.5 or 5 mg/kg/d, 5 d/wk for five weeks for Panc-1 tumor-bearing mice; IP; 10 mg/kg/d, 5 d/wk for three weeks for AsPC-1 tumor-bearing mice Experimental Results: Resulted in 56.1% and 82.5% inhibition of tumor growth in nude mice bearing Panc-1 orthotopic tumors, respectively. Dramatically suppressed the growth of AsPC-1 orthotopic tumors by 89.5% (P < 0.01) compared with the tumors in control animals. Led to almost complete tumor regression in MD242-treated mice in both models. |
| References |
[1]. Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for Pancreatic Cancer Therapy. Cancer Res. 2018 Oct 1;78(19):5656-5667. [2]. MDM2-NFAT1 dual inhibitor, MA242: Effective against hepatocellular carcinoma, independent of p53. Cancer Lett. 2019 Sep 10;459:156-167. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1462 mL | 10.7308 mL | 21.4615 mL | |
| 5 mM | 0.4292 mL | 2.1462 mL | 4.2923 mL | |
| 10 mM | 0.2146 mL | 1.0731 mL | 2.1462 mL |