ATB 346

ATB-346 is a novel hydrogen sulphide-releasing derivative of naproxen with markedly reduced toxicity.(In Vitro):Otenaproxesul (100 μM) inhibits human melanoma cell proliferation by inhibiting pro-survival pathways associated with NF-B and Akt activation.Otenaproxesul (100 μM) induces apoptosis of human melanoma cells.Otenaproxesul (100 M) causes inhibition of IkB degradation and of NF-kB nuclear translocation as demonstrated by a reduction in band intensity of the p65 subunit in A375 cells.(In Vivo):Otenaproxesul exhibits anti-inflammatory properties similar to naproxen, but with substantially reduced gastrointestinal toxicity.Otenaproxesul (orally, 43 μmol/kg) inhibits growth of melanoma tumors in vivo and reduce plasma levels of melanoma-associated chemokines.Otenaproxesul (orally, 16 mg/kg) results in significant inhibition of bone defect and other histological characteristics (such as flatness of the gingival epithelium, chronic inflammatory cell infiltration and loss of connective tissue in the gingival papillae). Otenaproxesul inhibits the increase of gingival IL-1β and IL-6 secondary to periodontitis, but IL-10 is unaffected.