Sepantronium hydrochloride (YM-155 hydrochloride) is a novel survivin suppressant that inhibits survivin promoter with an IC 50 of 0.54 nM[1].

Sepantronium bromide (YM155; 30 μM) is insensitive to survivn gene promoter-driven luciferase reporter activity. Sepantronium bromide shows significant supression on endogenous survivin expression in PC-3 and PPC-1 human HRPC cells with deficient p53 via transcriptional inhibition of the survivin gene promoter. Sepantronium bromide (100 nM) does not affect protein expression of c-IAP2, XIAP, Bcl-2, Bcl-xL, Bad, α-actin, and β-tubulin. Sepantronium bromide potently inhibits human cancer cell lines (mutated or truncated p53) such as PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5 and A375 with IC 50 s ranging from 2.3 to 11 nM, respectively [1]. Sepantronium bromide (YM155) resultin in an increase in sensitivity of NSCLC cells to γ-radiation. Sepantronium bromide combined with γ-radiation increases both the number of apoptotic cells and the activity of caspase-3. In addition, Sepantronium bromide delays the repair of radiation-induced double-strand breaks in nuclear DNA [2].

Sepantronium bromide (YM155; 3 and 10 mg/kg) inhibits the tumor growth in PC-3 xenografts, without significant body weight loss and blood cell count reduction. Sepantronium bromide is highly distributed to tumor tissue in vivo. Sepantronium bromide shows 80% TGI at a dose of 5 mg/kg in PC-3 orthotopic xenografts [1]. Sepantronium bromide (YM155) in combination with γ-radiation shows potent antitumor activity against H460 or Calu6 xenografts in nude mice [2]. In this orthotopic renal and metastatic lung tumors models, Sepantronium bromide (YM-155) and IL-2 additively decreases tumor weight, lung metastasis, and luciferin-stained tumor images [3].