22112-89-6

5,15-diphenylporphyrin (5,15-dpp) is a selective stat3-sh2 antagonist [1].stat3 is constitutively activated in many human cancers. stat3 functions as a critical mediator of oncogenic signaling through transcriptional activation of genes encoding apoptosis inhibitors, cell-cycle regulators and inducers of angiogenesis [2]. aberrant stat3 activity has been associated with transforming mechanisms induced by oncogenic tyrosine kinases [1].

5,15-dpp directly bound to stat3 and antagonized the function of stat3-sh2. 5,15-dpp selectively antagonized stat3-sh2 with an ic50 of 0.28 μm over the other sh2-containing proteins stat1 and grb2[1]. the estimated kd values for the 5,15-dpp binding to stat3 was 880 nm. treatment with 5,15-dpp suppressed the dna binding activity of stat3 in a concentration-dependent manner. 5,15-dpp poorly inhibited stat1 with an ic50 of 10 μm and showed no effect grb2 [1].

[1] uehara y, mochizuki m, matsuno k, et al. novel high-throughput screening system for identifying stat3–sh2 antagonists[j]. biochemical and biophysical research communications, 2009, 380(3): 627-631.
[2] jing n, tweardy d j. targeting stat3 in cancer therapy[j]. anti-cancer drugs, 2005, 16(6): 601-607.