Updated publication reference for PubMed record(s): 31844049. ProTargetMiner is the first publicly available expandable proteome signature library of anticancer molecules in cancer cell lines. The compounds cluster into groups by their proteomic signatures based on their targets and mechanisms. These can be deconvoluted by orthogonal partial least square (OPLS) modeling. Using 9 molecules representing most diverse action mechanisms, deep proteome datasets were built for 3 major cancer cell lines MCF-7, RKO and A549. Combining the data from the three cell lines identified common targets and mechanisms, while also highlighting important cell-specific differences. The database can be easily extended and merged with new compound signatures. We expect ProTargetMiner to serve as a valuable chemical proteomics resource catering primarily to the cancer research community, and become a popular tool in drug discovery. This submission includes the deep proteomics datasets in MCF-7 and RKO cell lines.