KI-20227

Cas：623142-96-1

Product Information：

KI-20227 is a potent and orally active inhibitor of c-Fms tyrosine kinase (M-CSFR, CSF1R) (IC50 values are 2, 12, 217 and 451 nM for c-Fms, VEGFR-2, PDGFRβ and c-Kit respectively). Ki20227 suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model. Ki20227 suppresses experimental autoimmune encephalomyelitis.

Chemical Formula: C24H24N4O5S

Exact Mass: 480.1467

Molecular Weight: 480.539

Elemental Analysis: C, 59.99; H, 5.03; N, 11.66; O, 16.65; S, 6.67

Synonym:

KI-20227

KI 20227

KI20227

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

Technical Data：

Appearance: Solid powder

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

In Vitro:

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.

In Vivo:

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.

References：

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.

Products are for research use only. Not for human use.