| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
NSC745885 targets EZH2 (enhancer of zeste homolog 2), a histone methyltransferase that is a component of the Polycomb repressive complex 2 (PRC2). EZH2 is involved in epigenetic gene silencing and is overexpressed in many cancers. By down-regulating EZH2 through proteasome-mediated degradation, NSC745885 reverses epigenetic silencing and induces cancer cell death.
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| 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].
In vitro, NSC745885 acts as a potent down-regulator of EZH2 through the proteasome degradation pathway. It induces G2/M cell-cycle arrest of cancer cells and degrades p53 via proteasome-dependent and -independent pathways. The compound shows selective toxicity against multiple cancer cell lines but not normal cells. |
| 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].
NSC745885 has demonstrated in vivo activity in preclinical models of cancer. It provides possibilities for the research of advanced bladder cancer and oral squamous cell carcinoma. Its anti-tumor activity is mediated through EZH2 down-regulation and induction of cell cycle arrest. |
| Enzyme Assay |
Cell-free assays for NSC745885 involve studying its effects on EZH2 protein levels and activity. These assays may use purified EZH2 protein or cell extracts to measure the compound's ability to induce EZH2 degradation via the proteasome pathway. The compound's effects on EZH2 methyltransferase activity can also be assessed.
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| 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. In vitro cellular assays for NSC745885 are performed using various cancer cell lines, including bladder cancer and oral squamous cell carcinoma cells. These assays measure the compound's ability to induce G2/M cell-cycle arrest, down-regulate EZH2, degrade p53, and reduce cell viability. Selective toxicity against cancer cells over normal cells is also assessed. |
| 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. In vivo animal studies for NSC745885 are conducted in mouse xenograft models of bladder cancer and oral squamous cell carcinoma. These studies typically involve administration of the compound, followed by assessment of tumor growth inhibition, EZH2 levels, and survival. The compound's anti-tumor efficacy and selectivity are evaluated in these models. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NSC745885 are characterized by its molecular properties: molecular formula C₁₄H₆N₂O₂S and molecular weight 266.27 g/mol. The compound is a small molecule anti-tumor agent. Its pharmacokinetic profile supports its use in preclinical research for bladder cancer and oral squamous cell carcinoma.
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| Toxicity/Toxicokinetics |
Toxicology studies of NSC745885 have been conducted to support its development as an anti-tumor agent. The compound shows selective toxicity against cancer cell lines but not normal cells, suggesting a favorable safety profile. Its toxicology profile includes effects on EZH2-mediated epigenetic regulation in normal tissues.
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| References | |
| Additional Infomation |
It has antitumor activity; the structure is shown in the first source.
NSC745885 (CAS: 4219-52-7) is an effective anti-tumor agent that shows selective toxicity against multiple cancer cell lines but not normal cells. It is a potent down-regulator of EZH2 through the proteasome-mediated degradation pathway. The compound has a molecular formula of C₁₄H₆N₂O₂S and a molecular weight of 266.27 g/mol. It is used for research of advanced bladder cancer and oral squamous cell carcinoma. |
| Molecular Formula |
C14H6N2O2S
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|---|---|
| Molecular Weight |
266.274641513824
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| Exact Mass |
266.01
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| CAS # |
4219-52-7
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| PubChem CID |
3835463
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
19
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| Complexity |
428
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1N=C2C=CC3C(C4C=CC=CC=4C(C=3C2=N1)=O)=O
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| InChi Key |
SJPXIVLTCBBWKT-UHFFFAOYSA-N
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| 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
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| Chemical Name |
naphtho[2,3-g][2,1,3]benzothiadiazole-6,11-dione
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| Synonyms |
NSC 745885 NSC-745885 NSC745885
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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) |
DMSO :< 1 mg/mL
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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 | 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 |
*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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