Synonym
KI-20227; KI 20227; KI20227.
IUPAC/Chemical Name
N-[4-[(6,7-Dimethoxy-4-quinolinyl)oxy]-2-methoxyphenyl]-N'-[1-(2-thiazolyl)ethyl]urea
InChi Key
SHPFDGWALWEPGS-UHFFFAOYSA-N
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)
SMILES Code
O=C(NC(C1=NC=CS1)C)NC2=CC=C(OC3=CC=NC4=CC(OC)=C(OC)C=C34)C=C2OC
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Ki20227 is an orally active and highly selective c-Fms tyrosine kinase (CSF1R) inhibitor with IC50s of 2 nM, 12 nM, 451 and 217 nM for CSF1R, VEGFR2 (vascular endothelial growth factor receptor-2), c-Kit (stem cell factor receptor) and PDGFRβ (platelet-derived growth factor receptor β). Ki20227 suppresses osteoclast differentiation and osteolytic bone destruction.
In vitro activity:
Ki20227 inhibited M-CSF-dependent reactions, such as lipopolysaccharide-induced tumor necrosis factor-alpha production, which were enhanced by M-CSF in vitro.
Reference: Eur J Immunol. 2008 Jan;38(1):283-91. https://pubmed.ncbi.nlm.nih.gov/18085662/
In vivo activity:
TP (triptolide) and Ki20227 pretreatments improved the neurobehavioral function in stroke mice. Synaptic protein expressions and density of dendritic spine density were upregulated in Ki20227 and TP pretreated stroke mice. Further, optimized integration of TP and Ki20227 pretreatments upregulated the NeuN expression and downregulated Iba1 expression after stroke.
Reference: Mediators Inflamm. 2020 Oct 31;2020:8796103. https://pubmed.ncbi.nlm.nih.gov/33192177/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
12.5 |
26.01 |
| DMSO |
54.8 |
113.96 |
| DMSO:PBS (pH 7.2) (1:3) |
0.3 |
0.52 |
| Ethanol |
3.0 |
6.24 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
480.54
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Ohno H, Uemura Y, Murooka H, Takanashi H, Tokieda T, Ohzeki Y, Kubo K, Serizawa I. The orally-active and selective c-Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model. Eur J Immunol. 2008 Jan;38(1):283-91. doi: 10.1002/eji.200737199. PMID: 18085662.
2. Ohno H, Kubo K, Murooka H, Kobayashi Y, Nishitoba T, Shibuya M, Yoneda T, Isoe T. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 2006 Nov;5(11):2634-43. doi: 10.1158/1535-7163.MCT-05-0313. PMID: 17121910.
3. Du X, Gao F, Chen S, Botchway BOA, Amin N, Hu Z, Fang M. Combinational Pretreatment of Colony-Stimulating Factor 1 Receptor Inhibitor and Triptolide Upregulates BDNF-Akt and Autophagic Pathways to Improve Cerebral Ischemia. Mediators Inflamm. 2020 Oct 31;2020:8796103. doi: 10.1155/2020/8796103. PMID: 33192177; PMCID: PMC7648715.
4. Du X, Xu Y, Chen S, Fang M. Inhibited CSF1R Alleviates Ischemia Injury via Inhibition of Microglia M1 Polarization and NLRP3 Pathway. Neural Plast. 2020 Aug 28;2020:8825954. doi: 10.1155/2020/8825954. PMID: 32908485; PMCID: PMC7474788.
In vitro protocol:
1. Ohno H, Uemura Y, Murooka H, Takanashi H, Tokieda T, Ohzeki Y, Kubo K, Serizawa I. The orally-active and selective c-Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model. Eur J Immunol. 2008 Jan;38(1):283-91. doi: 10.1002/eji.200737199. PMID: 18085662.
2. Ohno H, Kubo K, Murooka H, Kobayashi Y, Nishitoba T, Shibuya M, Yoneda T, Isoe T. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 2006 Nov;5(11):2634-43. doi: 10.1158/1535-7163.MCT-05-0313. PMID: 17121910.
In vivo protocol:
1. Du X, Gao F, Chen S, Botchway BOA, Amin N, Hu Z, Fang M. Combinational Pretreatment of Colony-Stimulating Factor 1 Receptor Inhibitor and Triptolide Upregulates BDNF-Akt and Autophagic Pathways to Improve Cerebral Ischemia. Mediators Inflamm. 2020 Oct 31;2020:8796103. doi: 10.1155/2020/8796103. PMID: 33192177; PMCID: PMC7648715.
2. Du X, Xu Y, Chen S, Fang M. Inhibited CSF1R Alleviates Ischemia Injury via Inhibition of Microglia M1 Polarization and NLRP3 Pathway. Neural Plast. 2020 Aug 28;2020:8825954. doi: 10.1155/2020/8825954. PMID: 32908485; PMCID: PMC7474788.
1: Aikawa Y, Yamagata K, Katsumoto T, Shima Y, Shino M, Stanley ER, Cleary ML, Akashi K, Tenen DG, Kitabayashi I. Essential role of PU.1 in maintenance of mixed lineage leukemia-associated leukemic stem cells. Cancer Sci. 2015 Mar;106(3):227-36. doi: 10.1111/cas.12593. Epub 2015 Feb 12. PubMed PMID: 25529853; PubMed Central PMCID: PMC4373983.
2: Toy EP, Lamb T, Azodi M, Roy WJ, Woo HH, Chambers SK. Inhibition of the c-fms proto-oncogene autocrine loop and tumor phenotype in glucocorticoid stimulated human breast carcinoma cells. Breast Cancer Res Treat. 2011 Sep;129(2):411-9. doi: 10.1007/s10549-010-1247-7. Epub 2010 Nov 10. PubMed PMID: 21063905.
3: Uemura Y, Ohno H, Ohzeki Y, Takanashi H, Murooka H, Kubo K, Serizawa I. The selective M-CSF receptor tyrosine kinase inhibitor Ki20227 suppresses experimental autoimmune encephalomyelitis. J Neuroimmunol. 2008 Mar;195(1-2):73-80. doi: 10.1016/j.jneuroim.2008.01.015. Epub 2008 Apr 2. PubMed PMID: 18378004.
4: Ohno H, Uemura Y, Murooka H, Takanashi H, Tokieda T, Ohzeki Y, Kubo K, Serizawa I. The orally-active and selective c-Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model. Eur J Immunol. 2008 Jan;38(1):283-91. PubMed PMID: 18085662.
5: Ohno H, Kubo K, Murooka H, Kobayashi Y, Nishitoba T, Shibuya M, Yoneda T, Isoe T. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 2006 Nov;5(11):2634-43. PubMed PMID: 17121910.
