Chemical Information

Biological Activity of XL228

XL228 is a protein kinase inhibitor targeting IGF1R, the Aurora kinases, FGFR1-3, ABL and SRC family kinases.
IC50 Value: 3 nM (Aurora A Kinase); 5 nM (Ki, Abl)[1]
Target: IGF1R; Aurora A; multikinase
in vitro: Approximately 30% of the lines demonstrated XL228 IC50 values of <100nM in viability assays, including many lines with characterized ALK or FGFR mutations or amplifications. Cell lines showing the highest level of response to XL228 were often sensitive to other Aurora, ALK or FGFR inhibitors as well. Sub-20nM activity was demonstrated against FGFR2 in a cellular kinase ELISA assay, and confirmed by immunoblot analysis. Potency against ALK in the cell kinase assay was lower (approximately200 nM) [2].
in vivo:
Clinical trial: Study of XL-228 in Subjects With Chronic Myeloid Leukemia or Philadelphia-Chromosome-Positive Acute Lymphocytic Leukemia. Phase 1
 

References on XL228

[1]. Scagliotti GV, et al. The role of the insulin-like growth factor signaling pathway in non-small cell lung cancer and other solid tumors. Cancer Treat Rev. 2012 Jun;38(4):292-302.

[2]. Douglas O. Clary, et al. Abstract C192: Characterization of the target profile of XL228, a multi-targeted protein kinase inhibitor in phase 1 clinical development. Molecular Cancer Therapeutics: December 2009; Volume 8, Issue 12, Supplement 1