Studies with knockout cells have suggested the importance of procaspase-7 as a secondary or alternate target for PAC-1, especially in the absence of procaspase-3. For example, experiments using mouse embryonic fibroblasts (MEFs) demonstrate that the double knockout of the CASP3 and CASP7 genes leads to cells that are insensitive to the proapoptotic effects of the PAC-1 class of compounds, and knocking in either CASP3 or CASP7 once again sensitizes these cells to PAC-1-type compounds. Recent experiments using cancer cell lines with CRISPR deletion of CASP3 are also consistent with this result. The activation of procaspase-7 by PAC-1 is consistent with biochemical data, although the relative importance of the procaspase-7 target in cells with functional procaspase-3 is uncertain.