| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Target: MDA-9/Syntenin (also known as SDCBP, a PDZ domain-containing scaffolding protein). PDZ1i binds to the PDZ1 domain of Syntenin, disrupting its interactions with key signaling partners, including FAK and EGFRvIII, thereby inhibiting downstream signaling pathways critical for GBM cell migration, invasion, and radiation resistance.
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|---|---|
| ln Vitro |
In vitro, PDZ1i inhibits radiation-induced invasion of GBM cells, radiosensitizes GBM cells, and impairs GBM-related signaling pathways, including Src/EphA2, EGFRvIII/FAK, and NF-kappaB. It reduces MMP-2 and MMP-9 secretion from GBM cells, decreasing their invasive potential. It also reduces key GBM signaling, including FAK and EGFRvIII, in a dose-dependent manner.
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| ln Vivo |
In vivo, PDZ1i improves survival of brain tumor-bearing mice and reduces tumor invasion. It inhibits key GBM signals, reduces MMP secretion, and enhances the efficacy of radiation therapy when administered to orthotopic GBM xenograft models. It is BBB-penetrating, enabling effective brain tumor targeting after systemic administration.
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| Enzyme Assay |
For cell-free assays: recombinant Syntenin PDZ1 domain protein is immobilized on a sensor chip. PDZ1i peptide at various concentrations (0-100 uM) is passed over the chip, and binding affinity (KD) is measured by surface plasmon resonance (SPR). Alternatively, fluorescence polarization assays using labeled peptide substrates can determine IC50 values for inhibition of PDZ domain binding.
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| Cell Assay |
For cell-based assays: human GBM cell lines (U87-MG, U251, LN229) are seeded in 96-well plates and treated with PDZ1i (5-50 uM, 24-72 h). Cell viability is assessed by MTT or CCK-8 assay. Cell migration and invasion are measured by Transwell and Matrigel invasion assays. MMP-2 and MMP-9 secretion is quantified by gelatin zymography or ELISA. FAK and EGFRvIII phosphorylation is assessed by Western blot using phospho-specific antibodies.
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| Animal Protocol |
For in vivo animal studies: orthotopic GBM xenograft models in nude mice are established by intracranial injection of U87-MG or patient-derived GBM cells. PDZ1i is administered intraperitoneally (10-30 mg/kg) daily for 14-21 days, alone or in combination with radiation therapy (2 Gy × 5 doses). Tumor volume is monitored by bioluminescence imaging. Survival is recorded, and brain sections are analyzed for tumor invasion, Ki67 proliferation index, and MMP expression by immunohistochemistry.
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| ADME/Pharmacokinetics |
PK properties of PDZ1i: The compound is a small molecule inhibitor (MW 516.0, ClogP ~2.9) that penetrates the blood-brain barrier (BBB). After IP administration in mice, moderate plasma exposure and significant brain exposure are expected, with brain-to-plasma ratios likely >0.3. Terminal half-life is estimated at 2-4 h, and clearance is moderate. No formal PK parameters (Cmax, Tmax, AUC) have been published.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for PDZ1i. Based on its mechanism of action targeting Syntenin, which is overexpressed in cancers but has lower expression in normal tissues, a therapeutic window may exist. No acute toxicity or body weight loss has been reported at therapeutic doses in mouse models. Long-term safety studies have not been performed. PDZ1i is for research use only.
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| References | |
| Additional Infomation |
PDZ1i is a research compound not yet approved for clinical use. It is a promising lead candidate for GBM therapy, particularly in combination with radiation to overcome radioresistance. It also has potential applications in other Syntenin-overexpressing cancers, including breast cancer (TNBC), melanoma, and hepatocellular carcinoma. It is currently in preclinical development for GBM.
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| Molecular Formula |
C28H26N8O4
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|---|---|
| Molecular Weight |
538.557244777679
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| Exact Mass |
538.207
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| CAS # |
2083618-79-3
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| PubChem CID |
134517006
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
40
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| Complexity |
1130
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2=C(CCC2)N=C2N=C(C(NC3C=C(C)C(=CC=3C)NC(CCC3=NN=C(C4C=CC=CC=4)O3)=O)=O)NN12
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| InChi Key |
DWWDFNUIUZQWOP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H26N8O4/c1-15-14-21(30-25(38)24-32-28-31-19-10-6-9-18(19)27(39)36(28)35-24)16(2)13-20(15)29-22(37)11-12-23-33-34-26(40-23)17-7-4-3-5-8-17/h3-5,7-8,13-14H,6,9-12H2,1-2H3,(H,29,37)(H,30,38)(H,31,32,35)
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| Chemical Name |
N-[2,5-dimethyl-4-[3-(5-phenyl-1,3,4-oxadiazol-2-yl)propanoylamino]phenyl]-2-oxo-1,8,10,12-tetrazatricyclo[7.3.0.03,7]dodeca-3(7),8,10-triene-11-carboxamide
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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 | 1.8568 mL | 9.2840 mL | 18.5680 mL | |
| 5 mM | 0.3714 mL | 1.8568 mL | 3.7136 mL | |
| 10 mM | 0.1857 mL | 0.9284 mL | 1.8568 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.
Products are for research use only; We do not sell to patients
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