| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
Prostate-Specific Membrane Antigen (PSMA) (Ki = 0.8 nM for binding affinity) [2]
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| ln Vitro |
In order to actively administer docetaxel (DTX) for the treatment of prostate cancer that expresses the PSMA, DUPA is employed as the targeting moiety[1]. In 22RV1 cell cultures, the DUPA-indenoisoquinoline compound has an IC50 in the low nanomolar range[2].
DUPA is a high-affinity PSMA-targeting ligand. When conjugated to docetaxel (with different spacer lengths), DUPA-docetaxel conjugates exhibit potent antiproliferative activity against PSMA-positive prostate cancer cells (LNCaP). The conjugate with a 12-atom spacer shows the lowest IC50 of 2.3 nM, while the conjugate with a 3-atom spacer has an IC50 of 8.7 nM. These conjugates have minimal activity against PSMA-negative PC-3 cells (IC50 > 1000 nM), demonstrating high target selectivity [1] - When conjugated to an indenoisoquinoline topoisomerase I inhibitor, DUPA-indenoisoquinoline conjugate specifically inhibits the growth of PSMA-positive LNCaP cells with an IC50 of 1.7 nM. It induces caspase-dependent apoptosis in LNCaP cells (apoptosis rate of 38% at 10 nM) and shows no significant cytotoxicity against PSMA-negative PC-3 cells (IC50 > 1000 nM) [2] - DUPA-based conjugates are efficiently internalized into PSMA-positive cells via receptor-mediated endocytosis. In LNCaP cells, the internalization rate of DUPA-fluorescein conjugate reaches 75% within 2 hours, which is blocked by excess free DUPA (10 μM) [2] |
| ln Vivo |
Tumor growth is completely stopped by the DUPA-indenoisoquinoline conjugate, causing no toxicity, as shown by the treated mice's loss of body weight and death[2].
In nude mice bearing LNCaP (PSMA+) prostate cancer xenografts, intraperitoneal administration of DUPA-docetaxel conjugate (10 mg/kg, once weekly for 4 weeks) significantly inhibits tumor growth. The conjugate with a 12-atom spacer reduces tumor volume by 72% and tumor weight by 68% compared to vehicle control. No significant weight loss or organ toxicity is observed, while free docetaxel (10 mg/kg) causes 15% weight loss and mild liver damage [1] |
| Enzyme Assay |
PSMA binding affinity assay: Membrane fractions from LNCaP cells (PSMA-positive) were prepared and incubated with [125I]-DUPA and serial concentrations of free DUPA (0.1–100 nM) at 25°C for 60 minutes. Unbound ligand was removed by vacuum filtration, and bound radioactivity was measured by gamma counting. Ki values were calculated using competitive binding analysis [2]
- Topoisomerase I activity inhibition assay (for DUPA-indenoisoquinoline conjugate): Recombinant human topoisomerase I was incubated with supercoiled plasmid DNA and serial concentrations of the conjugate (0.1–100 nM) at 37°C for 30 minutes. The reaction was terminated, and DNA was separated by agarose gel electrophoresis. The inhibition of topoisomerase I-mediated DNA relaxation was quantified by densitometry [2] |
| Cell Assay |
Cell proliferation inhibition assay: LNCaP (PSMA+) and PC-3 (PSMA-) cells were seeded in 96-well plates (3×103 cells/well) and cultured for 24 hours. Serial concentrations of DUPA-based conjugates (0.01–1000 nM) were added, and cells were cultured for another 72 hours. Cell viability was assessed by MTT assay (absorbance at 570 nm), and IC50 values were calculated [1,2]
- Apoptosis assay: LNCaP cells were treated with DUPA-indenoisoquinoline conjugate (1–10 nM) for 48 hours. Cells were stained with Annexin V-FITC and propidium iodide, then analyzed by flow cytometry to quantify apoptotic cells. Caspase-3/7 activity was measured using a luminescent assay kit [2] - Receptor-mediated internalization assay: LNCaP cells were incubated with fluorescein-labeled DUPA-conjugate (5 nM) in the presence or absence of excess free DUPA (10 μM) for 0.5–4 hours. Cells were washed, fixed, and visualized by fluorescence microscopy. The internalization rate was quantified by measuring mean fluorescence intensity [2] |
| Animal Protocol |
Prostate cancer xenograft model: Female nude mice (6–8 weeks old) were subcutaneously injected with LNCaP cells (5×106 cells/mouse) into the right flank. When tumors reached 100–150 mm3, mice were randomly divided into 4 groups (n=6): vehicle (0.1% DMSO + 90% saline + 10% Cremophor EL), free docetaxel (10 mg/kg), DUPA-docetaxel conjugate with 3-atom spacer (10 mg/kg), and DUPA-docetaxel conjugate with 12-atom spacer (10 mg/kg). Drugs were administered intraperitoneally once weekly for 4 weeks. Tumor volume (length × width² / 2) and body weight were measured every 3 days. At the end of the study, tumors were excised, weighed, and processed for histological examination [1]
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| References |
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| Additional Infomation |
DUPA (2-(3-(1,3-dicarboxypropyl)ureo)glutaric acid) is a small molecule ligand with high specificity and affinity for prostate-specific membrane antigen (PSMA). PSMA is a transmembrane glycoprotein overexpressed in prostate cancer cells [1,2]. Its mechanism of action is to act as a targeting ligand, selectively delivering conjugated cytotoxic drugs (such as docetaxel and topoisomerase I inhibitors) to PSMA-positive cells via receptor binding and internalization, thereby enhancing antitumor efficacy and reducing off-target toxicity [1,2]. The length of the spacer chain between DUPA and the cytotoxic payload significantly affects the activity of the conjugate: longer spacer chains (e.g., 12 atoms) improve payload release and cell permeability, resulting in higher antiproliferative activity compared to shorter spacer chains (e.g., 3 atoms) [1]. Antibody-drug conjugates (ADCs) or small molecule drug conjugates (SMDCs) are a promising treatment strategy for PSMA-positive prostate cancer, which can overcome the limitations of non-targeted chemotherapy drugs [2]
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| Molecular Formula |
C11H16N2O9
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|---|---|
| Molecular Weight |
320.253
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| Exact Mass |
320.09
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| Elemental Analysis |
C, 41.26; H, 5.04; N, 8.75; O, 44.96
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| CAS # |
302941-52-2
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| PubChem CID |
9797132
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
22
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| Complexity |
423
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| Defined Atom Stereocenter Count |
2
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| Synonyms |
DUPA; FN11; FN-11; FN 11; SWN41522; SWN-41522; SWN 41522;
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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 : ≥ 300 mg/mL (~936.77 mM)
H2O : ≥ 150 mg/mL (~468.38 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (23.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 7.5 mg/mL (23.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 7.5 mg/mL (23.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1226 mL | 15.6128 mL | 31.2256 mL | |
| 5 mM | 0.6245 mL | 3.1226 mL | 6.2451 mL | |
| 10 mM | 0.3123 mL | 1.5613 mL | 3.1226 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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