Methacycline (hydrochloride)

Methacycline hydrochloride is a tetracycline antibiotic and can inhibits bacterial protein synthesis. Methacycline hydrochloride is a potent epithelial-mesenchymal transition (EMT) inhibitor. Methacycline hydrochloride blocks EMT in vitro and fibrogenesis in vivo without directly affecting TGF-β1 Smad signaling. Methacycline hydrochloride is an antimicrobial and has the potential for pulmonary fibrosis^[1]. In Vitro: Methacycline hydrochloride is an inhibitor of A549 EMT with an IC50 of roughly 5 μM^[1].
In vitro, Methacycline hydrochloride (10, 20 μM; for 48 hours) inhibits TGF-β1-induced α-smooth muscle actin, Snail1, and collagen I of primary alveolar epithelial cells. Methacycline hydrochloride inhibits TGF-β1–induced non-Smad pathways, including c-Jun N-terminal kinase, p38, and Akt activation, but not Smad or β-catenin transcriptional activity. Methacycline has no effect on baseline c-Jun N-terminal kinase, p38, or Akt activities or lung fibroblast responses to TGF-β1^[1].
In Vivo: In vivo, Methacycline hydrochloride (100 mg/kg/day; ip; beginning 10 days after intratracheal Bleomycin) improves survival at Day 17. Bleomycin-induced canonical EMT markers, Snail1, Twist1, collagen I, as well as fibronectin protein and mRNA, ARE attenuated by Methacycline hydrochloride (Day 17)^[1].