Abstract: The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder associated with TGF?R1 activity, such as a cancer or fibrosis. The invention provides compounds of Formula (I) and Formula (II) as further described herein having an acidic moiety that enhances tissue specificity for targeted tissues and organs. The invention includes pharmaceutical compositions, pharmaceutical combinations, and methods of use of these compounds for treating conditions including cancer or fibrosis.