Signal transducer and activator of transcription 3 (STAT3) is a cytokine-inducible transcription factor with roles in inflammation and cancer. 5,15-DPP is a cell-permeable porphyrin derivative that selectively binds STAT3 (Kd = 880 nM). This inhibits STAT3 dimerization via Src homology 2 (Sh2) domains (IC50 = 280 nM), preventing nuclear translocation and DNA binding. 5,15-DPP poorly inhibits STAT1 (IC50 = 10 μM) and does not affect Grb2. It reduces IL-6-dependent STAT3 activation and consequent c-myc expression in MDA-MB-468 cells and blocks TRAIL-induced migration and invasion in A549 cells. Furthermore, inhibition of JAK/STAT signaling in satellite cells via 5,15-DPP and the JAK2 inhibitor AG-490 has been used to stimulate muscle regeneration in a model of aging skeletal muscle deterioration.
