| 中文名称 | Ki20227 |
| 英文名称 | N-[4-[(6,7-Dimethoxy-4-quinolinyl)oxy]-2-methoxyphenyl]-N'-[1-(2-thiazolyl)ethyl]urea |
| CAS号 | 623142-96-1 |
| 分子式 | C24H24N4O5S |
| 分子量 | 480.54 |
| EINECS号 | 200-258-5 |
| 沸点 | 621.8±55.0 °C(Predicted) |
| 密度 | 1.327 |
| 溶解度 | DMSO 中≥48.1 mg/mL；不溶于水；温和加热和超声波下，乙醇中≥8.6 mg/mL |
| 形态 | 棕色粉末。 |
| 酸度系数(pKa) | 12.03±0.46(Predicted) |
| 颜色 | 米白色至粉红色 |
N-[4-[(6,7-二甲氧基-4-喹啉基)氧基]-2-甲氧基苯基]-N'-[1-(2-噻唑基)乙基]脲是一种 c-fms 酪氨酸激酶抑制剂，可在骨转移模型中抑制破骨细胞分化和溶骨性骨破坏。
Ki20227 是一种口服活性的 c-Fms tyrosine kinase(CSF1R) 的高选择性抑制剂，对 c-Fms、vascular endothelial growth factor receptor-2 (KDR/VEGFR-2)、stem cell factor receptor (c-Kit) 和 platelet-derived growth factor receptor beta (PDGFRβ) 的IC50值为2 nM、12 nM、451 nM和217 nM。| Target | Value |
|
c-Fms
(Cell-free assay) | 2 nM |
|
VEGFR2
(Cell-free assay) | 12 nM |
|
PDGFRβ
(Cell-free assay) | 217 nM |
|
c-Kit
(Cell-free assay) | 451 nM |
Ki20227 (0.1-1000 nM; 72 hours) with 100 and 1,000 nM almost suppresses M-NFS-60 cell growth and HUVEC cell growth, respectively.
Ki20227 (0.1-1000 nM; 1 hour) suppresses M-CSF-dependent c-Fms phosphorylation in a dose-dependent manner.
Cell Viability Assay
| Cell Line: | M-NFS-60 cells, HUVEC cells, human A375 melanoma cells |
| Concentration: | 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM |
| Incubation Time: | 72 hours |
| Result: | 100 and 1,000 nM almost suppressed M-NFS-60 cell growth and HUVEC cell growth, respectively. |
Cell Viability Assay
| Cell Line: | RAW264.7 cell lysate |
| Concentration: | 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM |
| Incubation Time: | 1 hour |
| Result: | Suppressed M-CSF-dependent c-Fms phosphorylation in a dose-dependent manner. |
Ki20227 (orally;10-50 mg/kg/d for 20 days) of 50 mg/kg/d of Ki20227 for 20 days markedly decreases the osteolytic lesion areas.
ki20227 during global ischemia led to a significant deficit in microglial density in the CNS in mice, and CSF1R-inhibition led to a significant reduction in the neuronal density of mice.
| Animal Model: | 4-week-old male F344/NJcl-rnu rats |
| Dosage: | 10, 20, and 50 mg/kg |
| Administration: | Orally; once per day for 20 days |
| Result: | Oral administration of 50 mg/kg/d markedly decreased the osteolytic lesion areas. |