For research use only. Not for therapeutic Use.
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[1][2].
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)[2].
Plogosertib (0-4 μΜ, 2 h) reduces phosphorylation of the PLK1 substrate, pSer4-nucleophosmin (p-NPM) in KYSE-410 cells[2].
Plogosertib (100 nM, 24 h) increases in the proportion of mitotic cells, with increased monopolar spindles in HeLa cells[2].
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)[2].
Plogosertib (CYC140, oral administration, 40 mg/kg, qd 5/2/5) inhibits tumor growth in preclinical xenograft models of acute leukemia and solid tumors[2].
Plogosertib (Coumpond A7, 1 mg/kg, mouse) shows pharmacokinetic parameters: Cmax (453 ng/mL), AUC (377 hr•ng/mL), Cl (2445 mL/h/kg)[3].
| Catalog Number | I043392 |
| CAS Number | 1137212-79-3 |
| Synonyms | 4-[(9-cyclopentyl-5-methyl-6-oxospiro[8H-pyrimido[4,5-b][1,4]diazepine-7,1′-cyclopropane]-2-yl)amino]-3-methoxy-N-[4-(4-methylpiperazin-1-yl)cyclohexyl]benzamide |
| Molecular Formula | C34H48N8O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C34H48N8O3/c1-39-16-18-41(19-17-39)25-11-9-24(10-12-25)36-31(43)23-8-13-27(29(20-23)45-3)37-33-35-21-28-30(38-33)42(26-6-4-5-7-26)22-34(14-15-34)32(44)40(28)2/h8,13,20-21,24-26H,4-7,9-12,14-19,22H2,1-3H3,(H,36,43)(H,35,37,38) |
| InChIKey | UFNLNMWVOMFWGS-UHFFFAOYSA-N |
| SMILES | CN1CCN(CC1)C2CCC(CC2)NC(=O)C3=CC(=C(C=C3)NC4=NC=C5C(=N4)N(CC6(CC6)C(=O)N5C)C7CCCC7)OC |
| Reference | [1]. Sylvie Moureau, et al. Abstract 4178: The novel PLK1 inhibitor, CYC140: Identification of pharmacodynamic markers, sensitive target indications and potential combinations. Cancer Res (2017) 77 (13_Supplement): 4178. [2]. Moureau S, et al. Therapeutic potential of novel PLK1 inhibitor CYC140 in esophageal cancer and acute leukemia[J]. European Journal of Cancer, 2016, 1(69): S117. [3]. Susan Davis, et al. Treatment of proliferative diseases with pyrimidodiazepinones. Patent US20150320762A1. |
