XL184 is a pan tyrosine kinase inhibitor that primarily targets VEGFR2 (IC50 = 0.035 nM) and c-Met (IC50 = 1.3 nM) but also inhibits RET, c-Kit, Axl, FLT3, and Tie2 (IC50s = 5.2, 4.6, 7, 11.3, and 14.3 nM, respectively). In in vivo breast, lung, and glioma tumor models that represent dysregulated c-Met and VEGFR signaling, XL184 was shown to reduce tumor and endothelial cell proliferation, inhibiting both angiogenesis and metastasis. XL184 has undergone clinical trial in a broad number of cancers, including thyroid carcinoma, prostate cancer, ovarian cancer, melanoma, breast cancer, non-small cell lung cancer, hepatocellular cancer, renal cell carcinoma, and glioblastoma.
