streptonigrin

Streptonigrin is a natural aminoquinone antibiotic isolated from *Streptomyces flocculus* with potent antineoplastic activity. Its primary historical mechanism involves redox cycling to generate superoxide and hydroxyl radicals, leading to extensive DNA strand scission and inhibition of DNA synthesis. Recent research has highlighted its role as a pharmacological inhibitor of Transglutaminase 2 (TGase 2), specifically disrupting the interaction between the N-terminus of TGase 2 and GSK3β. This disruption promotes the autophagic degradation of GSK3β and stabilizes β-catenin, thereby reversing the epithelial-mesenchymal transition (EMT) phenotype associated with drug resistance and metastasis in ovarian cancer. Although it showed significant activity in early clinical trials for lymphomas and various solid tumors, its clinical use was curtailed by profound and prolonged myelosuppression.

Brand names

Nigrin

Other names

bruneomycin