| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
ZS34 (10 days) inhibited the proliferation of MTAP-deficient cells (NCI-H838, NCI-H1437, MCF-7, MDA-MB-231 and MIA PaCa-2 cells) with IC50 values of 1.70, 386, 38.1, 37.2 and 115 nM, respectively. It also showed selectivity for cells with normal MTAP function (A-375, AsPC-1, DU145, NCI-H460 and NCI-H520) with IC50 >10000 nM[1]. ZS34 (10 days) showed a strong antiproliferative effect on MTAP-deficient HCT116 cells (IC50 = 124 nM), but weaker activity against WT HCT116 cells (IC50 > 10000 nM), showing excellent selective inhibitory effect with a selectivity index (SI) of over 80.6[1]. ZS34 (0-10 μM; 96 h) selectively induces DNA damage in MTAP-deficient HCT116 cells by inhibiting MAT2A[1]. ZS34 binds to the allosteric site of the MAT2A dimer, forms hydrogen bonds with Arg313 and coordinated water molecules, and performs π-π stacking with Phe20, Trp274 and Phe18, while its ortho-methyl group participates in the CH-π interaction with Phe333[1].
|
|---|---|
| ln Vivo |
ZS34 (10 and 30 mg/kg, orally, once daily for 30 days) showed strong in vivo antitumor efficacy and good safety profile in the HCT116 MTAP-/- xenograft model [1]. ZS34 (400 mg/kg, orally, single dose) showed no significant toxicity in mice [1].
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: HCT116 (MTAP-/-) and HCT116 (WT) Tested Concentrations: 0, 0.1, 1 μM Incubation Duration: 96 h Experimental Results: Induced a dose-dependent decrease in the SDMA level, in HCT116 MTAP-/- cells, but not in HCT116 WT cells. Induced a marked increase in γH2AX levels, a marker of DNA damage, in HCT116 MTAP-/- cells, but not in HCT116 WT cells. Immunofluorescence[1] Cell Types: HCT116 (MTAP-/-) and HCT116 (WT) Tested Concentrations: 0.1, 1, 10 μM Incubation Duration: 96 h Experimental Results: led to a marked increase in γH2AX levels in HCT116 MTAP-/-cells compared to the control, but not in HCT116 WT cells. |
| Animal Protocol |
Animal/Disease Models: Female ALB/c nude mice subcutaneously inoculated with HCT116 MTAP-/- cells[1]
Doses: 10, 30 mg/kg Route of Administration: p.o., daily for 30 days Experimental Results: Significantly suppressed tumor growth, with tumor growth inhibition (TGI) values of 57.3% and 89.0% at 10 and 30 mg/kg, respectively. Showed a tendency to cause tumor regression at 30 mg/kg. Reduced SAM levels in tumors. Showed no significant body weight loss compared to control. Animal/Disease Models: ICR mice[1] Doses: 400 mg/kg Route of Administration: p.o., single dose Experimental Results: Was well tolerated at this high dose. |
| References |
| Molecular Formula |
C18H14CLN3O2
|
|---|---|
| Molecular Weight |
339.78
|
| CAS # |
3106086-17-0
|
| Appearance |
Typically exists as solids at room temperature
|
| 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)
|
| 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
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 | 2.9431 mL | 14.7154 mL | 29.4308 mL | |
| 5 mM | 0.5886 mL | 2.9431 mL | 5.8862 mL | |
| 10 mM | 0.2943 mL | 1.4715 mL | 2.9431 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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