Plogosertib

Research use only, not for human use.

Plogosertib (CYC140) is an orally active, selective, potent, and ATP-competitive PLK1 inhibitor with an IC50 value of 3 nM.

Plogosertib (CYC140) is a selective, potent, and orally active ATP-competitive PLK1 inhibitor (IC50: 3 nM). Plogosertib is an anti-cancer agent with anti-proliferative activity. Plogosertib can be used in the research of several tumors, including esophageal, gastric, leukemia, non–small cell lung cancer, ovarian, and squamous cell cancers.

Plogosertib (CYC140) selectively inhibits PLK1 (IC50: 3 nM), and is >50 fold more potent against PLK2 and PLK3 (IC50s: 149 nM and 393 nM, respectively).Plogosertib (0-4 μΜ, 2 h) reduces phosphorylation of the PLK1 substrate, pSer4-nucleophosmin (p-NPM) in KYSE-410 cells.Plogosertib (100 nM, 24 h) increases in the proportion of mitotic cells, with increased monopolar spindles in HeLa cells.Plogosertib (72 h) preferentially inhibits cell proliferation in malignant cell lines (IC50s: 14-21 nM), and is less toxic against none-malignant cell lines (IC50: 82 nM).:Cell Proliferation Assay Cell Line:KYSE-410 cells Concentration:0, 0.07, 0.15, 0.3, 0.6, 1.25 μΜ Incubation Time:72 h Result:Inhibited cell proliferation in a concentration-dependent manner.Western Blot Analysis Cell Line:KYSE-410 cells Concentration:0, 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4 μΜ Incubation Time:2 h (p-NPM), 24 h (p-HH3), 72 h (cPARP) Result:Reduced phosphorylation of the PLK1 substrate (p-NPM).Increased in the mitotic marker pSer10 histone H3 (p-HH3), and the cleavage of PARP (cPARP, an indicator of cell death).

Plogosertib (CYC140, oral administration, 40 mg/kg, qd 5/2/5) inhibits tumor growth in preclinical xenograft models of acute leukemia and solid tumors.Plogosertib (Coumpond A7, 1 mg/kg, mouse) shows pharmacokinetic parameters: Cmax (453 ng/mL), AUC (377 hr?ng/mL), Cl (2445 mL/h/kg).Animal Model:HL60 promyelocytic leukemia xenograft Dosage:40, 54, 67 mg/kg, qd 5/2/5 Administration:Oral administration Result:Inhibited tumor growth (>87%) without significant loss in body weight.Animal Model:OE19 esophageal xenograft Dosage:40 mg/kg, qd 5/2 Administration:Oral administration Result:Inhibited tumor growth (61 % inhibition).

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Cell Cycle/DNA Damage

PLK

PLK

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1137212-79-3

616.797

C34H48N8O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (162.13 mM; Ultrasonic )

O=C1C2(CN(C=3C(N1C)=CN=C(NC4=C(OC)C=C(C(N[C@@H]5CC[C@H](CC5)N6CCN(C)CC6)=O)C=C4)N3)C7CCCC7)CC2

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(-20℃)

With Ice Pack

≥ 2 years