Plogosertib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Plogosertib (CYC140) 是一种选择性的、有效的、具有口服活性的 ATP 竞争性的 PLK1 抑制剂 (IC50: 3 nM)。Plogosertib 是一种有抗增殖活性的抗癌剂，可用于多种肿瘤的研究，包括食管癌、胃癌、白血病、非小细胞肺癌、卵巢癌和鳞状细胞癌。

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 中的溶解度 : 100 mg/mL (162.13 mM; 超声助溶 )

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