PNU-142586
Based on 1 Customer Validation
PNU-142586 is the major metabolite of Linezolid (HY-10394). PNU-142586 can inhibit the activity of DNA topoisomerase 2-α (TOP2A) and DNA topoisomerase 2-β (TOP2B). PNU-142586 interferes with DNA replication and transcription by blocking the binding of DNA to TOP2 and inhibiting ATP hydrolysis, ultimately leading to antiproliferative and cytotoxic effects, including mitochondrial dysfunction. PNU-142586 can be used to study Linezolid-induced hematotoxicity and its molecular mechanism.
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- Pureza : 96.44%
- No. CAS: 368891-70-7
- Fòrmula: C16H20FN3O6
- Peso molecular:369.34
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Almacenamiento:
-20°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
topoisomerase II alpha |
topoisomerase II beta |
In Vitro
PNU-142586 (0.1-2.5 mM; 30 min) potently inhibits human TOP2A-mediated kDNA decatenation in a cell-free system with an IC50 of ~150 μM[1].
PNU-142586 (0.1-2.5 mM; 30 min) inhibits human TOP2A-mediated scDNA relaxation in a cell-free system with an IC50 of ~1.425 mM[1].
PNU-142586 (0.1-2.5 mM; 30 min) potently inhibits human TOP2B-mediated kDNA decatenation in a cell-free system with an IC50 of ~150 μM[1].
PNU-142586 (sodium) (0.1-2.5 mM; 30 min) inhibits human TOP2B-mediated scDNA relaxation in a cell-free system with an IC50 of ~1.875 mM[1].
PNU-142586 (31.25-500 μM) directly binds to the human TOP2A DNA binding domain with a Kd of 310.6 ± 89.2 μM, as measured by tryptophan fluorescence quenching[1].
PNU-142586 (31.25-500 μM) directly binds to the human TOP2A ATPase domain with a Kd of 300.8 ± 31.3 μM, as measured by tryptophan fluorescence quenching[1].
PNU-142586 (50 nM-100 μM; 144 hours) suppresses proliferation of human HL-60 promyelocytes in a concentration-dependent manner, with up to ~25% inhibition at 100 μM after 144 hours[1].
PNU-142586 (50 nM-100 μM; 144 h) induces concentration-dependent cytotoxicity and inhiibits proliferation in human HL-60 promyelocytes and THP-1 monocytes[1].
PNU-142586 (50 nM-100 μM; 0-120 h) suppresses mitochondrial MT-CO1 gene transcription, gene and protein expression in human HL-60 promyelocytes and and THP-1 monocytes at concentrations ≥5 μM and incubation times ≥48 h[1].
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:Human HL-60 promyelocytes, Human THP-1 monocytes
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Concentration:50, 500 nM, 5, 50, 100 μM
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Incubation Time:144 h
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Result:Suppressed HL-60 and THP-1 cell proliferation in a concentration-dependent manner.
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Cell Line:Human HL-60 promyelocytes, Human THP-1 monocytes
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Concentration:50, 500 nM, 5, 50, 100 μM
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Incubation Time:0-120 h
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Result:Down-regulated MT-CO1 transcription at concentrations above 5 μM and after incubation periods of more than 48 h, with a more pronounced effect than Linezolid (HY-10394).
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Cell Line:Human HL-60 promyelocytes, Human THP-1 monocytes
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Concentration:50, 500 nM, 5, 50, 100 μM
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Incubation Time:144 h
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Result:Suppressed MT-CO1 protein levels, with a more pronounced effect than Linezolid.
In Vivo
PNU-142586 (0.0005-0.5 mM; incubation; from 24 hpf to 120 hpf) induces dose-dependent pericardial edema in Danio rerio embryos and suppresses mitochondrial mt-co1 gene expression at concentrations ≥0.5 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:wild-type (female, V-VI X. laevis oocytes)[1]
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Dosage:0.125 mM (46.17 mg/liter); 0.25 mM (92.34 mg/liter); 0.5 mM (184.67 mg/liter); 1 mM (369.34 mg/liter)
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Administration:incubation; 168 h
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Result:Induced a dose-dependent increase in oocyte malformation, with a ~43% malformation rate at 0.5 mM compared to no malformation in vehicle controls.
Dose-dependently inhibited kDNA decatenation activity in Xenopus oocyte extracts, with partial inhibition observed at 0.5 mM.
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Animal Model:wild-type (embryos)[1]
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Dosage:0.0005 mM (0.18 mg/liter); 0.005 mM (1.85 mg/liter); 0.025 mM (9.23 mg/liter); 0.125 mM (46.17 mg/liter); 0.25 mM (92.34 mg/liter); 0.5 mM (184.67 mg/liter)
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Administration:incubation; from 24 hpf to 120 hpf
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Result:Induced a dose-dependent increase in pericardial edema in zebrafish embryos, with effects visible at 72 hpf and peaking at 96 hpf in the 0.125 to 0.25 mM groups.
Significantly down-regulated mt-co1 gene expression at both 72 and 120 hpf compared to vehicle controls, with stable expression levels between 72 and 120 hpf, at concentrations ≥0.5 μM.
Chemical Information
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No. CAS 368891-70-7
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Appearance Solid
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Peso molecular 369.34
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Fòrmula C16H20FN3O6
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Color White to off-white
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SMILES
O=C(CN(CCO)C1=CC=C(C=C1F)N2C(O[C@H](C2)CNC(C)=O)=O)O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
-20°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
Solvente y solubilidad
In Vitro:
H2O : ≥ 100 mg/mL (270.75 mM)
* "≥" means soluble, but saturation unknown.
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 (protect from light, 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.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
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 (protect from light, 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.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Protocolo
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PCNA Immunodetection Proliferation Assay
PCNA immunodetection measures proliferative activity by detecting proliferating cell nuclear antigen, a nuclear protein associated with DNA polymerase δ function and DNA replication. The assay readout is the proportion of PCNA-positive nuclei among total counted cells, but PCNA labeling is not identical to BrdU labeling because PCNA can mark late G1/early S-associated replication competence and may persist beyond active DNA synthesis depending on fixation and extraction conditions.
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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
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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.
Pureza y Documentación
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Ficha de datos (282 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
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 (protect from light, 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 |
|---|---|---|---|---|---|
| H2O | 1 mM | 2.7075 mL | 13.5377 mL | 27.0753 mL | 67.6883 mL |
| 5 mM | 0.5415 mL | 2.7075 mL | 5.4151 mL | 13.5377 mL | |
| 10 mM | 0.2708 mL | 1.3538 mL | 2.7075 mL | 6.7688 mL | |
| 15 mM | 0.1805 mL | 0.9025 mL | 1.8050 mL | 4.5126 mL | |
| 20 mM | 0.1354 mL | 0.6769 mL | 1.3538 mL | 3.3844 mL | |
| 25 mM | 0.1083 mL | 0.5415 mL | 1.0830 mL | 2.7075 mL | |
| 30 mM | 0.0903 mL | 0.4513 mL | 0.9025 mL | 2.2563 mL | |
| 40 mM | 0.0677 mL | 0.3384 mL | 0.6769 mL | 1.6922 mL | |
| 50 mM | 0.0542 mL | 0.2708 mL | 0.5415 mL | 1.3538 mL | |
| 60 mM | 0.0451 mL | 0.2256 mL | 0.4513 mL | 1.1281 mL | |
| 80 mM | 0.0338 mL | 0.1692 mL | 0.3384 mL | 0.8461 mL | |
| 100 mM | 0.0271 mL | 0.1354 mL | 0.2708 mL | 0.6769 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
PNU-142586 Related Classifications
HY-123393 Related Classifications
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