NSC745885 (NSC-745885) is a novel and potent down-regulator of EZH2 with anti-tumor activity. It induces the down-regulation of EZH2 via proteasome-mediated degradation.
Physicochemical Properties
| Molecular Formula | C14H6N2O2S |
| Molecular Weight | 266.274641513824 |
| Exact Mass | 266.01 |
| CAS # | 4219-52-7 |
| PubChem CID | 3835463 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 19 |
| Complexity | 428 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1N=C2C=CC3C(C4C=CC=CC=4C(C=3C2=N1)=O)=O |
| InChi Key | SJPXIVLTCBBWKT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C14H6N2O2S/c17-13-7-3-1-2-4-8(7)14(18)11-9(13)5-6-10-12(11)16-19-15-10/h1-6H |
| Chemical Name | naphtho[2,3-g][2,1,3]benzothiadiazole-6,11-dione |
| Synonyms | NSC 745885 NSC-745885 NSC745885 |
| 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
| ln Vitro | NSC745885 (0.5–4 μM; 24, 48, or 72 hours) dramatically lowers the densities of cultivated cells in comparison to untreated cells, either by encouraging death or inhibiting proliferation in SAS cells. After 72 hours of therapy, NSC745885's IC50 is 0.85 μM[1]. The effects of NSC745885 (0.5–4 μM; 24 hours) on annexin V positive cells are dose-dependent and show dose-dependent differences[1]. In SAS cells, NSC745885 (0.5-2 μM; 24 or 48 hours) raises protein levels and reduces XIAP protein levels in a dose-dependent manner[1]. |
| ln Vivo | When compared to the vehicle control, NSC745885 (intraperitoneal injection; 2 mg/kg; once daily; 10 days) treatment dramatically reduces tumor size and shows better safety than doxorubicin[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: SAS cells is obtained from a poorly differentiated human squamous cell carcinoma Tested Concentrations: 0.5 μM, 1 μM, 1.5 μM, 2 μM, 4 μM Incubation Duration: 24, 48, or 72 hrs (hours) Experimental Results: Decreases SAS cells growth as a time and dose-dependent manner. Apoptosis Analysis[1] Cell Types: SAS cells is obtained from a poorly differentiated human squamous cell carcinoma Tested Concentrations: 0.5 μM, 1 μM, 1.5 μM, 2 μM, 4 μM Incubation Duration: 24 hrs (hours) Experimental Results: Decreases SAS cells growth as a time and dose-dependent manner. Western Blot Analysis[1] Cell Types: SAS cells is obtained from a poorly differentiated human squamous cell carcinoma Tested Concentrations: 0.5 μM, 1 μM, 1.5 μM, 2 μM Incubation Duration: 24 or 48 hrs (hours) Experimental Results: Increased cleaved caspase-3 expression and diminished XIAP expression. |
| Animal Protocol |
Animal/Disease Models: Eightweeks old NOD/SCID (NOD.CB17 Prkdcscid/J) mice[1] Doses: 2 mg/kg Route of Administration: intraperitoneal (ip)injection; 2 mg/kg; one time/day; 10 days Experimental Results: Inhibited engrafted tumors growth in vivo. |
| References |
[1]. A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.PLoS One. 2014 Aug 15;9(8):e104703. [2]. Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo.Oncotarget. 2014 Nov 15;5(21):10342-55. |
Solubility Data
| Solubility (In Vitro) | DMSO :< 1 mg/mL |
| 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 | 3.7556 mL | 18.7779 mL | 37.5559 mL | |
| 5 mM | 0.7511 mL | 3.7556 mL | 7.5112 mL | |
| 10 mM | 0.3756 mL | 1.8778 mL | 3.7556 mL |