Aurintricarboxylic acid (TREX1 inhibitor Compound 296, NSC4056) is a potent, bioactive inhibitor of
cystathionine γ-lyase (CSE) with IC5 of 0.6 uM, also is a selective inhibitor of the
TWEAK-Fn14 signaling pathway, also specifically inhibits
TREX1 DNase with IC50 of 0.463 uM for rhTREX1.
TREX1 inhibitor Compound 296 (Compound #296, Aurintricarboxylic acid) also specifically inhibits TREX1 DNase with IC50 of 0.463 uM for rhTREX1, with no activity against DNase I.
TREX1 inhibitor Compound 296 induced type I IFN signaling in cancer cells, and inhibited tumor growth in mice in an inteferon alpha/beta receptor (IFNAR)-dependent manner, also stimulated T-cell infiltration into tumors and synergized with immune checkpoint blockade.
NSC4056 (Aurintricarboxylic acid) selectively binds to Arg and Tyr residues of CSE active site and preferably inhibits the CSE activity in cells rather than cystathionine β-synthase (CBS), the other H2S-generating enzyme.
NSC4056 dose-dependently inhibits endogenous CSE activity and decreases the H2S content in Raw264.7 macrophages.
Aurintricarboxylic acid is an inhibitor of topoisomerase II and apoptosis.
Aurintricarboxylic acid is a selective inhibitor of the TWEAK-Fn14 signaling pathway.
Aurintricarboxylic acid also stimulates tyrosine phosphorylation processes including the Jak2/STAT5 pathway in NB2 lymphoma cells, ErbB4 in neuroblastoma cells, and MAP kinases, Shc proteins, phosphatidylinositide 3-kinase and phospholipase Cγ in PC12 cells.
