| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C16H20FN3O6 |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
PNU-142586 is the major metabolite of Linezolid. It can inhibit the activity of DNA topoisomerase 2-α (TOP2A) and DNA topoisomerase 2-β (TOP2B), interfering with DNA replication and transcription by blocking DNA binding to TOP2 and inhibiting ATP hydrolysis, which leads to antiproliferative and cytotoxic effects, including mitochondrial dysfunction. It can be used to study Linezolid-induced hematotoxicity and its molecular mechanism[1]. It is supplied as a white to off-white solid (C16H20FN3O6, MW 369.34).
Physical & Chemical Properties
| CAS Number | 368891-70-7 |
|---|---|
| Molecular Formula | C16H20FN3O6 |
| Molecular Weight | 369.34 g/mol |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | O=C(CN(CCO)C1=CC=C(C=C1F)N2C(O[C@H](C2)CNC(C)=O)=O)O |
| Target | Topoisomerase II alpha, Topoisomerase II beta |
| Signaling Pathway | Cell Cycle/DNA Damage |
| Solubility | In Vitro: H2O: ≥ 100 mg/mL (270.75 mM) * "≥" means soluble, but saturation unknown. |
| Storage | -20°C, protect from light, stored under nitrogen. In solvent: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| H2O | ≥ 100 mg/mL (270.75 mM) | — |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); protect from light, stored under nitrogen; avoid repeated freeze-thaw cycles.
If water is used as the stock solvent, dilute to the working solution and sterilize it through a 0.22 μm filter before use.
Data provided by the manufacturer.
In Vitro
PNU-142586 (0.1-2.5 mM; 30 min) strongly inhibits human TOP2A-mediated kDNA decatenation in a cell-free system, with an IC50 of ~150 μM[1]. In a cell-free system, PNU-142586 (0.1-2.5 mM; 30 min) also inhibits human TOP2A-mediated scDNA relaxation, with an IC50 of ~1.425 mM[1]. Human TOP2B-mediated kDNA decatenation is strongly inhibited by PNU-142586 (0.1-2.5 mM; 30 min) in a cell-free system, with an IC50 of ~150 μM[1]. In a cell-free system, PNU-142586 (sodium) (0.1-2.5 mM; 30 min) inhibits human TOP2B-mediated scDNA relaxation, with an IC50 of ~1.875 mM[1]. PNU-142586 (31.25-500 μM) binds directly to the human TOP2A DNA binding domain (Kd of 310.6 ± 89.2 μM), measured by tryptophan fluorescence quenching[1]. Direct binding to the human TOP2A ATPase domain is also seen for PNU-142586 (31.25-500 μM), with a Kd of 300.8 ± 31.3 μM by tryptophan fluorescence quenching[1]. Proliferation of human HL-60 promyelocytes is suppressed concentration-dependently by PNU-142586 (50 nM-100 μM; 144 hours), with inhibition of up to ~25% at 100 μM after 144 hours[1]. PNU-142586 (50 nM-100 μM; 144 h) causes concentration-dependent cytotoxicity and inhibits proliferation of human HL-60 promyelocytes and THP-1 monocytes[1]. At concentrations ≥5 μM and incubation times ≥48 h, PNU-142586 (50 nM-100 μM; 0-120 h) suppresses mitochondrial MT-CO1 gene transcription, gene expression and protein expression in human HL-60 promyelocytes and THP-1 monocytes[1].
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. |
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) causes dose-dependent morphological toxicity in Xenopus laevis oocytes, and also inhibits topoisomerase II-mediated kDNA decatenation; malformation appears in ~43% of oocytes at 0.5 mM[1]. In Danio rerio embryos, PNU-142586 (0.0005-0.5 mM; incubation; from 24 hpf to 120 hpf) causes dose-dependent pericardial edema and suppresses mitochondrial mt-co1 gene expression at concentrations ≥0.5 μM[1].
| 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. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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