9353 blocked RhoA activity in cells, and inhibited RhoA‐associated breast cancer cell activity synergistically with 48 (Figure 16). However, 53 contains a PAINs motif; the pyrazolidin‐3,5‐diones are potent Michael acceptors.45a, 45b Hence, even though there is evidence for 53 acting on LARG in vitro, off‐target binding should be explored before this compound is considered suitable as a probe or therapeutic. The gene discussed is RHOA; the disease is breast cancer.