KI-20227

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). KI-20227 suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. KI-20227 inhibits disease progression in a collagen-induced arthritis mouse model. KI-20227 suppresses experimental autoimmune encephalomyelitis.

Product information

CAS Number: 623142-96-1

Molecular Weight: 480.54

Formula: C24H24N4O5S

Synonym:

KI 20227

KI20227

KI-20227

Chemical Name: N-[4-[(6,7-Dimethoxy-4-quinolinyl)oxy]-2-methoxyphenyl]-N'-[1-(2-thiazolyl)ethyl]urea

Smiles: COC1=CC2C(=CC=NC=2C=C1OC)OC1=CC(OC)=C(C=C1)NC(=O)NC(C)C1=NC=CS1

InChiKey: SHPFDGWALWEPGS-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 96 mg/mL(199.77 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

KI-20227 (0.1-1000 nM; 72 hours) with 100 and 1, 000 nM almost suppresses M-NFS-60 cell growth and HUVEC cell growth, respectively. KI-20227 (0.1-1000 nM; 1 hour) suppresses M-CSF-dependent c-Fms phosphorylation in a dose-dependent manner.

In Vivo:

KI-20227 (orally;10-50 mg/kg/d for 20 days) of 50 mg/kg/d of KI-20227 for 20 days markedly decreases the osteolytic lesion areas. KI-20227 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. 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.
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. 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.