The present invention provides fused pyrimidine compounds of the general Formula (I): or a salt thereof, wherein the variables are as defined in the specification. Fused pyrimidine compounds of the general Formula (I) are provided as kinase inhibitors, such as multi-kinase inhibitors. In one aspect, fused pyrimidine compounds of the general Formula (I) are provided as IGF-IR inhibitors. The compounds may be used in a method of treating cancer. Pharmaceutical compositions containing a fused pyrimidine compounds of the general Formula (I) and a pharmaceutically acceptable carrier are also provided, as are kits containing a fused pyrimidine compound of the general Formula (I) or salt thereof and instructions for use, e.g., in a method of treating cancer.