PNU-142586
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.
For research use only. We do not sell to patients.
- CAS No.: 368891-70-7
- Formula: C16H20FN3O6
- Molecular Weight:369.34
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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All Topoisomerase Isoforms
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Biological Activity
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topoisomerase II alpha |
topoisomerase II beta |
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.
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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.
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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CAS No. 368891-70-7
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Molecular Weight 369.34
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Formula C16H20FN3O6
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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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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