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^[1]. 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 K_d 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 K_d 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]. 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].