PNU-159682
Based on 1 Customer Validation
PNU-159682, a metabolite of the anthracycline Nemorubicin, is a highly potent DNA topoisomerase II inhibitor with excellent cytotoxicity. PNU-159682 acts as a more potent and tolerated ADC cytotoxin than Doxorubicin for ADC synthesis. PNU-159682 can be used in EDV-nanocell technology to overcome agent resistance.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 98.50%
- CAS 番号: 202350-68-3
- 分子式: C32H35NO13
- 分子量:641.62
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保管条件:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
製品説明
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Daunorubicins/Doxorubicins |
Topoisomerase I |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | EC50 |
0.37 pM
Compound: 1; PNU-159682
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Cytotoxicity against HEK293T cells assessed as reduction in cell viability
Cytotoxicity against HEK293T cells assessed as reduction in cell viability
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[PMID: 33127540] |
| MES-SA | EC50 |
0.2 pM
Compound: 1; PNU-159682
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Cytotoxicity against human MES-SA cells assessed as reduction in cell viability
Cytotoxicity against human MES-SA cells assessed as reduction in cell viability
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[PMID: 33127540] |
| MES-SA/Dx5 | EC50 |
0.38 pM
Compound: 1; PNU-159682
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Cytotoxicity against human MES SA/DX5 cells assessed as reduction in cell viability
Cytotoxicity against human MES SA/DX5 cells assessed as reduction in cell viability
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[PMID: 33127540] |
体外実験
PNU-159682 (0-500 nM; exposed to the compounds for 1 hour and then cultured in compound-free medium for 72 hours) has cytotoxic effects on human tumor cell lines in a sulforhodamine B assay. The IC70 values are 0.577 nM, 0.39 nM, 0.128 nM, and 0.081 nM, 0.086 nM and 0.075 nM for HT-29, A2780, DU145, EM-2, Jurkat and CEM cells, respectively[1]. It against human tumor cell lines with IC70 in the ranging 68 nM-578 nM and 181 nM-1717 nM towards MMDX and doxorubicin, respectively[1].? PNU-159682 is more potent than MMAE on NHL cell lines. In a cell viability assay, PNU-159682 is against BJAB.Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 with IC50 values of 0.10 nM, 0.020 nM, 0.055 nM, and 0.1 nM, respectively. While MMAE is against BJAB.Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 with IC50 values of 0.54 nM, 0.25 nM, 1.19 nM and 0.25 nM, respectively[2].PNU-159682 is thousands of times more cytotoxic than doxorubicin and can be used to develop a new class of ADCs. PNU159682?to?anti-CD22?antibody (anti-CD22-NMS249) exhibits strong anti-tumor effects in vitro. Anti-CD22-NMS249 (PNU159682?to?anti-CD22?antibody) is active in in vitro viability assays of NHL cell lines and is 2 to 20 fold more potent than pinatuzumab vedotin, the ADC anti-CD22-NMS249 is against BJAB.Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 with IC50 values of 0.058 nM, 0.030 nM, 0.0221 nM, and 0.01 nM, respectively[3].PNU-159682 (100 μM) weakly inhibits topoisomerase II unknotting activity. PNU-159682 shows cytotoxic effect on CAIX-expressing SKRC-52 cells with IC50 of 25 nM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HT-29, A2780, DU145, EM-2, Jurkat and CEM cells
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Concentration:0-500 nM
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Incubation Time:Exposed to the PNU-159682 for 1 hour and then cultured in compound-free medium for 72 hours
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Result:Was 2,360- to 790-fold and 6,420- to 2,100-fold more potent than MMDX and doxorubicin, respectively. Exhibited IC70 values of PNU-159682 are in the subnanomolar range (0.07-0.58 nM) and noticeably lower than that recorded for both MMDX and doxorubicin.
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Four- to six-week-old female CD-1 athymic nude mice with MX-1 tumor fragments[1]
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Dosage:4 μg/kg
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Administration:Intravenous injection; q7dx3; 40 days
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Result:Exhibited anti-cancer effects in MX-1 human mammary carcinoma xenografts to PNU-159682.
化学情報
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CAS 番号 202350-68-3
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性状 Solid
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分子量 641.62
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分子式 C32H35NO13
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Color Red to reddish brown
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SMILES
COC1=C(C(C(C(O)=C([C@@H](O[C@H]2C[C@H]3[C@H](O[C@H]4N3CCO[C@@H]4OC)[C@H](C)O2)C[C@@](C(CO)=O)(O)C5)C5=C6O)=C6C7=O)=O)C7=CC=C1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
溶剤 & 溶解度
体外:
DMSO : 100 mg/mL (155.86 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
体内:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.90 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
純度とドキュメンテーション
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データシート (288 KB)
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SDS (584 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Quintieri L, et al. Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes. Clin Cancer Res. 2005 Feb 15;11(4):1608-17. [Content Brief]
[2]. Cazzamalli S, et al. Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to Renal Cell Carcinoma. Mol Cancer Ther. 2016 Dec;15(12):2926-2935. [Content Brief]
[3]. Pengxuan Zhao, et al. Recent advances of antibody drug conjugates for clinical applications. Acta Pharm Sin B. 2020 Sep;10(9):1589-1600. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.5586 mL | 7.7928 mL | 15.5855 mL | 38.9639 mL |
| 5 mM | 0.3117 mL | 1.5586 mL | 3.1171 mL | 7.7928 mL | |
| 10 mM | 0.1559 mL | 0.7793 mL | 1.5586 mL | 3.8964 mL | |
| 15 mM | 0.1039 mL | 0.5195 mL | 1.0390 mL | 2.5976 mL | |
| 20 mM | 0.0779 mL | 0.3896 mL | 0.7793 mL | 1.9482 mL | |
| 25 mM | 0.0623 mL | 0.3117 mL | 0.6234 mL | 1.5586 mL | |
| 30 mM | 0.0520 mL | 0.2598 mL | 0.5195 mL | 1.2988 mL | |
| 40 mM | 0.0390 mL | 0.1948 mL | 0.3896 mL | 0.9741 mL | |
| 50 mM | 0.0312 mL | 0.1559 mL | 0.3117 mL | 0.7793 mL | |
| 60 mM | 0.0260 mL | 0.1299 mL | 0.2598 mL | 0.6494 mL | |
| 80 mM | 0.0195 mL | 0.0974 mL | 0.1948 mL | 0.4870 mL | |
| 100 mM | 0.0156 mL | 0.0779 mL | 0.1559 mL | 0.3896 mL |
PNU-159682 関連分類
HY-16700 関連分類
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