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Gastrin‐releasing peptide receptor (GRPr) plays proliferative and inflammatory roles in living systems. Here, we report a highly selective GRPr antagonist (JMV594)‐tethered iridium(III) complex for probing GRPr in living cancer cells and immune cells. This probe exhibited desirable photophysical properties and also displayed negligible cytotoxicity, overcoming the inherent toxicity of the iridium(III) complex. Its long emission lifetime enabled its luminescence signal to be readily distinguished from the interfering fluorescence of organic dyes by using a time‐resolved technique. This probe selectively visualized living cancer cells via specific binding to GRPr, while it also modulated the function of GRPr on TNF‐α secretion in immune cells. To our knowledge, this is the first peptide‐conjugated iridium(III) complex developed as a GRPr bioimaging probe and modulator of GRPr activity. This theranostic agent shows great potential at unmasking the diverse roles of GRPr in living systems. [ABSTRACT FROM AUTHOR]

Abstract: Prolyl‐isomerase 1 (Pin1) is a conserved enzyme that regulates cell processes such as cell cycle progression, transcriptional regulation, and apoptosis. However, overexpression of Pin1 is correlated with a higher probability of prostate tumor recurrence. We utilized a molecular docking technique to identify Pin1 inhibitors from a database of natural product and natural product‐like compounds. The action of the hit compounds against Pin1 activity was studied using multiple methods, including a fluorometric enzymatic assay, co‐immunoprecipitation, western blotting, cell thermal shiftm, and other techniques. We have identified compound 1 as a natural‐product‐like inhibitor of Pin1 activity via structure‐based virtual screening and showed that compound 1 could target Pin1 and disrupt the interaction between Pin1 and the p65 subunit of NF‐κB in cells. Furthermore, compound 1 reduced nuclear p65 (Thr254) phosphorylation and attenuated NF‐κB activity in cells. Finally, compound 1 induced apoptosis in prostate cancer cells. Compound 1 represents a natural product‐like Pin1 inhibitor that acts via targeting the Pin1–NF‐κB interaction. [ABSTRACT FROM AUTHOR]