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KI-20227 is a potent and orally bioavailable inhibitor of c-Fms tyrosine kinase (M-CSFR, CSF1R) (IC50 are 2, 12, 217 and 451 nM for c-Fms, VEGFR-2, PDGFRβ and c-Kit respectively). In a model of bone metastasis, Ki20227 inhibits the differentiation of osteoclasts and the destruction of osteolytic bone. Ki20227 slows the advancement of the disease in a mouse model of collagen-induced arthritis. Experimental autoimmune encephalomyelitis is suppressed by Ki20227.
| Targets |
CSF1R (IC50 = 2 nM); VEGFR2 (IC50 = 12 nM); c-Kit (IC50 = 451 nM); PDGFRβ (IC50 = 217 nM)
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|---|---|
| ln Vitro |
Ki20227 is a novel quinoline-urea derivative that inhibits the tyrosine kinase of c-Fms. It is discovered that Ki20227 has inhibitory concentrations of 2, 12, 451, and 217 nmol/L for c-Fms, vascular endothelial growth factor receptor-2 (KDR), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor B, respectively. Moreover, Ki20227 has been shown to suppress M-CSF-dependent M-NFS-60 cell growth in vitro, but not M-CSF-independent A375 human melanoma cell growth. Moreover, Ki20227 dose-dependently suppresses the growth of tartrate-resistant acid phosphatase-positive osteoclast-like cells in an osteoclast-like cell formation assay employing mouse bone marrow cells.[1]
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| ln Vivo |
In vivo experiments using nude rats administering oral Ki20227 after intracardiac injection of A375 cells show suppression of osteoclast-like cell accumulation and bone resorption caused by metastatic tumor cells. Furthermore, in rats that have had their ovaries removed, Ki20227 reduces the quantity of osteoclast-like cells that are acid phosphatase-positive and resistant to tartrate on the surfaces of their bones. The results of this study indicate that Ki20227 suppresses osteoclast accumulation in vivo caused by M-CSF, thereby inhibiting osteolytic bone destruction.[1]
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| Cell Assay |
The 96-well culture plate is seeded with M-NFS-60, HUVEC, and A375 cells, which are then cultured for a full day. Following this, culture media are swapped out and left to incubate for an additional 72 hours, either with or without Ki20227 (0.1–3,000 nmol/L).
For 12 hours, RAW264.7 cells are serum starved in DMEM with 0.1% FCS. The cells are then treated with serial dilutions of Ki20227 and allowed to incubate for an hour. AVC 264. For four minutes, seven cells are stimulated with 50 ng/mL of recombinant mouse M-CSF. The RAW264 protein contains c-Fms. An ice-cold lysis buffer is used to prepare the 7 cell lysate. |
| Animal Protocol |
Athymic rats (F344/NJcl-rnu), Sprague-Dawley rats
20 mg/kg Oral gavage |
| References |
| Molecular Formula |
C24H24N4O5S
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|---|---|
| Molecular Weight |
480.539
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| Exact Mass |
480.1467
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| Elemental Analysis |
C, 59.99; H, 5.03; N, 11.66; O, 16.65; S, 6.67
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| CAS # |
623142-96-1
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| Related CAS # |
623142-96-1
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| Appearance |
Solid powder
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| SMILES |
CC(C1=NC=CS1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)OC
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| InChi Key |
SHPFDGWALWEPGS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N4O5S/c1-14(23-26-9-10-34-23)27-24(29)28-17-6-5-15(11-20(17)30-2)33-19-7-8-25-18-13-22(32-4)21(31-3)12-16(18)19/h5-14H,1-4H3,(H2,27,28,29)
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| Chemical Name |
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea
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| Synonyms |
KI20227; KI-20227; KI 20227
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 62.5~96 mg/mL (130.1~199.8 mM)
Water: ˂1 mg/mL Ethanol: ~3 mg/mL (~6.2 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0810 mL | 10.4050 mL | 20.8099 mL | |
| 5 mM | 0.4162 mL | 2.0810 mL | 4.1620 mL | |
| 10 mM | 0.2081 mL | 1.0405 mL | 2.0810 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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