AS101

AS101, also known as Ossirene, is a synthetic non-toxic tellurium derivative, structurally similar to cisplatin, with immuno-modulating, antiviral, and hair growth-promoting activities. Ammonium trichlorotellurate may inhibit the inflammatory cytokine interleukin-10 (IL-10) and may induce hematopoietic cells to express interleukin-2 (IL-2), IL-2 receptors, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, tumor necrosis factor (TNF) and interferons (INFs). This agent is also a potent inducer of IL-1 and IL-6. Accordingly, ammonium trichlorotellurate may protect against chemotherapy-induced myelosuppression. In addition, this agent exhibits hair growth-promoting activity by inducing anagen production and inhibiting catagen production, resulting in the promotion of follicular keratinocyte proliferation and interference with follicular keratinocyte terminal differentiation, respectively. Accordingly, ammonium trichlorotellurate may protect against chemotherapy-induced alopecia.(In Vitro):Ossirene (AS101; 1 μg/mL; for 24 hours) almost completely abrogates expression of pStat3. Ossirene may reduce expression of Bcl-2 after inhibition of Stat3 activation via IL-10 inhibition.AS101 (0.5, 5 mg/mL; 24 hours) inhibits IL-1β-induced mRNA expression of inflammatory mediators in the RPE in a dose-dependent manner. AS101 inhibits IL-1β-induced mRNA expression and protein production of IL-6 and IL-8 in RPE cells. AS101 (5 mg/mL; 1 hour) inhibits the phosphorylation of the p65 component of the NFκB complex activated by IL-1β.Ossirene (0.1, 0.5, 1, 2.5 μg/mL) significantly decreases B16 melanoma, stomach adenocarcinoma, and human glioblastoma multiforme (GBM) cells proliferation.AS101 (0.5 μg/mL; for 24 hours) sensitizes GBM tumor cells to paclitaxel in an IL-10-dependent manner.(In Vivo):Ossirene (AS101; 0.5 mg/kg/day; IP; 25 days) sensitizes GBM tumors to paclitaxel via inhibition of IL-10, resulting in increased survival.