Ki20227

Catalog No.S7688 Batch:S768801

Technical Data

Formula	C₂₄H₂₄N₄O₅S
Molecular Weight	480.54	CAS No.	623142-96-1
Solubility (25°C)*	In vitro	DMSO	96 mg/mL (199.77 mM)
		Ethanol	3 mg/mL (6.24 mM)
		Water	˂1 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Ki20227 is an orally active and highly selective inhibitor of c-Fms tyrosine kinase(CSF1R) with IC50 of 2 nM, 12 nM, 451 nM and 217 nM for c-Fms, vascular endothelial growth factor receptor-2 (KDR/VEGFR-2), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor beta (PDGFRβ), respectively.

Targets

c-Fms ^[1] (Cell-free assay)	VEGFR2 ^[1] (Cell-free assay)	PDGFRβ ^[1] (Cell-free assay)	c-Kit ^[1] (Cell-free assay)
2 nM	12 nM	217 nM	451 nM

In vitro

Ki20227, a novel quinoline-urea derivative, is a c-Fms tyrosine kinase inhibitor. The IC50s of Ki20227 to inhibit c-Fms, vascular endothelial growth factor receptor-2 (KDR), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor B are found to be 2, 12, 451, and 217 nmol/L, respectively. Ki20227 is also found to inhibit the M-CSFdependent growth of M-NFS-60 cells but not the M-CSFindependent growth of A375 human melanoma cells in vitro. Furthermore, in an osteoclast-like cell formation assay using mouse bone marrow cells, Ki20227 inhibits the development of tartrate-resistant acid phosphatase-positive osteoclast-like cells in a dose-dependent manner.^[1]

In vivo

In in vivo studies, oral administration of Ki20227 suppresses osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. Moreover, Ki20227 decreases the number of tartrate-resistant acid phosphatase–positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats. These findings suggest that Ki20227 inhibits osteolytic bone destruction through the suppression of M-CSF-induced osteoclast accumulation in vivo.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines RAW264.7, M-NFS-60, A375, HUVEC cells Concentrations 0.1 nM - 3000 nM Incubation Time 72 h, 1h Method M-NFS-60, HUVEC, and A375 cells are seeded on a 96-well culture plate and cultured for 24 hours. Then, culture mediums are changed and incubated for a further 72 hours in the presence or absence of Ki20227 (0.1–3,000 nmol/L). RAW264.7 cells are serum starved for 12 hours in DMEM containing 0.1% FCS. Serial dilutions of Ki20227 are then added to the cells, and they are incubated for 1 hour. RAW264.7 cells are stimulated with 50 ng/mL of recombinant mouse M-CSF for 4 minutes. c-Fms protein in the RAW264.7 cell lysate is prepared with ice-cold lysis buffer.
Animal Study:^{^[1]}	Animal Models Athymic rats (F344/NJcl-rnu), Sprague-Dawley rats Dosages 20 mg/kg Administration Oral gavage

Cell Assay:^{^[1]}

Cell lines
RAW264.7, M-NFS-60, A375, HUVEC cells
Concentrations
0.1 nM - 3000 nM
Incubation Time
72 h, 1h
Method
M-NFS-60, HUVEC, and A375 cells are seeded on a 96-well culture plate and cultured for 24 hours. Then, culture mediums are changed and incubated for a further 72 hours in the presence or absence of Ki20227 (0.1–3,000 nmol/L).
RAW264.7 cells are serum starved for 12 hours in DMEM containing 0.1% FCS. Serial dilutions of Ki20227 are then added to the cells, and they are incubated for 1 hour. RAW264.7 cells are stimulated with 50 ng/mL of recombinant mouse M-CSF for 4 minutes. c-Fms protein in the RAW264.7 cell lysate is prepared with ice-cold lysis buffer.

Animal Study:^{^[1]}

Animal Models
Athymic rats (F344/NJcl-rnu), Sprague-Dawley rats
Dosages
20 mg/kg
Administration
Oral gavage

References

[1] Hiroaki Ohno, et al. Mol Cancer Ther. 2006 Nov;5(11):2634-43.

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SHIPPING AND STORAGE
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