2. Antibody-drug Conjugate/ADC Related Cell Cycle/DNA Damage
  3. ADC Cytotoxin Topoisomerase
  4. PNU-159682

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.

For research use only. We do not sell to patients.

PNU-159682 Chemical Structure

PNU-159682 Chemical Structure

CAS No. : 202350-68-3

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5 mg USD 251 In-stock
10 mg USD 440 In-stock
25 mg USD 924 In-stock
50 mg USD 1430 In-stock
100 mg USD 2200 In-stock
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Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of PNU-159682:

PNU-159682 Related Antibodies

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Topoisomerase Topo I Topo II

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

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.

IC50 & Target[1][2]

Daunorubicins/Doxorubicins

 

Topoisomerase I

 

In Vitro

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.

PNU-159682 Related Antibodies

Cell Viability Assay[2]

Cell Line: HT-29, A2780, DU145, EM-2, Jurkat and CEM cells
Concentration: 0-500 nM
Incubation Time: Exposed to the PNU-159682 for 1 hour and then cultured in compound-free medium for 72 hours
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.
In Vivo

PNU-159682 (single-dose; i.v.15 μg/kg) is a maximum tolerated dose in murine L1210 leukemia model. PNU-159682 shows an improved antitumor activity in vivo. The antitumor effect of PNU-159682 (increase in life span=29%) is comparable to that afforded by 90 μg/kg MMDX (increase in life=36%)[1].
PNU-159682 (i.v. 4 μg/kg; q7dx3; 40 days) has a therapeutic response in MX-1 human mammary carcinoma mice. What’s more, from day 39, four out of seven mice receiving PNU-159682 exhibits complete tumor regression[1].
PNU-159682 is 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 vivo. ADC dose (anti-CD22-NMS249; 50 μg/m2 conjugated PNU-159682) is well tolerated in mice and results in less than 10% weight loss[2].
In the BJAB.Luc model the efficacy of antiCD22-NMS249 (single dose; 2 mg/kg) is similar to anti-CD22-vc-MMAE. At 2 mg/kg dosage, antiCD22-NMS249 gives complete remission of the tumors (NMS249: 110-134%TGI vs. vc-MMAE: 114-143%TGI). Additionally, a single dose of antiCD22-NMS249 at 2 mg/kg results in tumor stasis for three weeks[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Four- to six-week-old female CD-1 athymic nude mice with MX-1 tumor fragments[1]
Dosage: 4 μg/kg
Administration: Intravenous injection; q7dx3; 40 days
Result: Exhibited anti-cancer effects in MX-1 human mammary carcinoma xenografts to PNU-159682.
Molecular Weight

641.62

Formula

C32H35NO13
CAS No.
Appearance

Solid

Color

Reddish Brown to red

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility
In Vitro: 

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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.5586 mL 7.7928 mL 15.5855 mL
5 mM 0.3117 mL 1.5586 mL 3.1171 mL
View the 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.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 2.5 mg/mL (3.90 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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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% 
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: 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)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation

Purity: 98.25%

COA (262 KB) HNMR (293 KB) LCMS (268 KB)

Handling Instructions (2659 KB)
References

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
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PNU-159682 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PNU-159682202350-68-3PNU159682PNU 159682ADC CytotoxinTopoisomeraseADC PayloadADCs ToxinNMS249EDV nanocellnon-Hodgkin’s lymphomaNHLacute myeloid leukemiaAMLInhibitorinhibitorinhibit

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