| Identification | Back Directory | [Name]
Benzamide, 4-[(9'-cyclopentyl-8',9'-dihydro-5'-methyl-6'-oxospiro[cyclopropane-1,7'-[7H]pyrimido[4,5-b][1,4]diazepine]-2'(5'H)-yl)amino]-3-methoxy-N-[trans-4-(4-methyl-1-piperazinyl)cyclohexyl]- | [CAS]
1137212-79-3 | [Synonyms]
plogosertib
Benzamide, 4-[(9'-cyclopentyl-8',9'-dihydro-5'-methyl-6'-oxospiro[cyclopropane-1,7'-[7H]pyrimido[4,5-b][1,4]diazepine]-2'(5'H)-yl)amino]-3-methoxy-N-[trans-4-(4-methyl-1-piperazinyl)cyclohexyl]- | [Molecular Formula]
C34H48N8O3 | [MOL File]
1137212-79-3.mol | [Molecular Weight]
616.81 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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]. | Animal Model: | HL60 promyelocytic leukemia xenograft[2] | | 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[2] | | Dosage: | 40 mg/kg, qd 5/2 | | Administration: | Oral administration | | Result: | Inhibited tumor growth (61 % inhibition). |
| [IC 50]
PLK1: 3 nM (IC50); PLK2: 149 nM (IC50); PLK3: 393 nM (IC50) | [References]
[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. |
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