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

PNU-159682 

Cat. No.: HY-16700 Purity: 97.24%
Handling Instructions

PNU-159682, a metabolite of the anthracycline nemorubicin, is a highly potent DNA topoisomerase I 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 drug resistance.

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

PNU-159682 Chemical Structure

PNU-159682 Chemical Structure

CAS No. : 202350-68-3

Size Price Stock Quantity
5 mg USD 750 In-stock
Estimated Time of Arrival: December 31
10 mg USD 1000 In-stock
Estimated Time of Arrival: December 31
50 mg USD 2400 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 1 publication(s) in Google Scholar

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  • Biological Activity

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Description

PNU-159682, a metabolite of the anthracycline nemorubicin, is a highly potent DNA topoisomerase I inhibitor with excellent cytotoxicity[1]. PNU-159682 acts as a more potent and tolerated ADC cytotoxin than Doxorubicin for ADC synthesis[2]. PNU-159682 can be used in EDV-nanocell technology to overcome drug resistance[3].

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].

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

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].

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.
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)

*"≥" means soluble, but saturation unknown.

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
10 mM 0.1559 mL 0.7793 mL 1.5586 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 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

  • 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

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (3.90 mM); Clear solution

*All of the co-solvents are provided by MCE.
References

Purity: 97.24%

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PNU-159682
Cat. No.:
HY-16700
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