2. Cell Cycle/DNA Damage
  3. Topoisomerase
  4. 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.

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PNU-142586

PNU-142586 Chemical Structure

CAS No. : 368891-70-7

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PNU-142586 Related Antibodies

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Description

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[1].

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.

PNU-142586 Related Antibodies

Cell Cytotoxicity Assay[1]

Cell Line: Human HL-60 promyelocytes, Human THP-1 monocytes
Concentration: 50, 500 nM, 5, 50, 100 μM
Incubation Time: 144 h
Result: Suppressed HL-60 and THP-1 cell proliferation in a concentration-dependent manner.

Real Time qPCR[1]

Cell Line: Human HL-60 promyelocytes, Human THP-1 monocytes
Concentration: 50, 500 nM, 5, 50, 100 μM
Incubation Time: 0-120 h
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).

Western Blot Analysis[1]

Cell Line: Human HL-60 promyelocytes, Human THP-1 monocytes
Concentration: 50, 500 nM, 5, 50, 100 μM
Incubation Time: 144 h
Result: Suppressed MT-CO1 protein levels, with a more pronounced effect than Linezolid.
In Vivo

PNU-142586 (0.015625-1 mM; incubation; 168 h) induces dose-dependent morphological toxicity in Xenopus laevis oocytes and inhibits topoisomerase II-mediated kDNA decatenation, with ~43% of oocytes showing malformation at 0.5 mM[1].
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.

Animal Model: wild-type (female, V-VI X. laevis oocytes)[1]
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)
Administration: incubation; 168 h
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.
Animal Model: wild-type (embryos)[1]
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)
Administration: incubation; from 24 hpf to 120 hpf
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.
Molecular Weight

369.34

Formula

C16H20FN3O6
CAS No.
SMILES

O=C(CN(CCO)C1=CC=C(C=C1F)N2C(O[C@H](C2)CNC(C)=O)=O)O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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PNU-142586 Related Classifications

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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-142586368891-70-7PNU142586PNU 142586TopoisomeraseLZDTOP2ATOP2BHL-60 cellsTHP-1 cellsCYP450Inhibitorinhibitorinhibit

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