| Chemical Properties | Back Directory | [Boiling point ]
644.5±65.0 °C(predicted) | [density ]
1.380±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [pka]
9.55±0.20(predicted) |
| Hazard Information | Back Directory | [Uses]
PLK1-IN-10 (Compound 4Bb) is an orally active PLK1 PBD (polo-box domain) inhibitor. PLK1-IN-10 blocks the interaction of PLK1 with the cell division regulator protein 1 (PRC1) and decreases the protein expression of the CDK1-Cyclin B1 complex. PLK1-IN-10 reacts with glutathione (GSH) to increase cellular oxidative stress, ultimately leading to cell death[1]. | [in vivo]
PLK1-IN-10 (30, 50 mg/kg; i.p.; every two days for 32 days) significantly inhibits tumor growth in A549/DDP drug-resistant xenograft mice, with the 50 mg/kg group even causing tumor regression[1].
PLK1-IN-10 (30 mg/kg; p.o.; every two days for 20 days) effectively inhibits tumor growth in NCI-H1975 drug-resistant xenograft mice[1].
| Animal Model: | A549/DDP drug-resistant xenograft mice[1] | | Dosage: | 30, 50 mg/kg | | Administration: | i.p.; once every two days for 32 days | | Result: | TGI reached 42% for the 30 mg/kg group and 62% for the 50 mg/kg group.
Extended the median survival time from 38 days in the control group to 53 days in the 30 mg/kg group and 62 days in the 50 mg/kg group.
Had no significant impact on the body weight and major organs of the mice, except for a slight difference in heart index observed in the 30 mg/kg group.
Significantly reduced the number of Ki-67 positive cells in the tumor tissue.
Showed no significant differences in H&E staining of major organs, further confirming its good biosafety. |
| Animal Model: | NCI-H1975 drug-resistant xenograft mice[1] | | Dosage: | 30 mg/kg | | Administration: | p.o.; once every two days for 20 days | | Result: | TGI reached 44%. Caused no harm to the body weight and major organs of the mice. |
| [IC 50]
PLK1 PBD | [References]
[1] Li P, Li Y, et al. Identification of naphthalimide-derivatives as novel PBD-targeted polo-like kinase 1 inhibitors with efficacy in drug-resistant lung cancer cells. Eur J Med Chem. 2024 May 5;271:116416. DOI:10.1016/j.ejmech.2024.116416 |
|
|