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AS101 was shown to have several anti-tumor and bone marrow sparing activities in vitro, in vivo and in clinical trials. These include sensitization of solid tumors to chemotherapy and preventing Chemotherapy Induced Thrombocytopenia (CIT); sensitization of leukemic cells from AML patients to chemotherapy and anti-angiogenic activity that can inhibit the metastatic process.

Phase I and Phase II clinical trials with dozens of cancer patients with advanced malignancies (lung carcinoma, melanoma, sarcoma, ovarian carcinoma, hypernephroma, breast carcinoma, testicular carcinoma, bladder carcinoma, gastric carcinoma and brain tumor) were conducted under FDA approved INDs. AS101 was proven to be safe for human use with minimal toxicity and showed no serious adverse events.

The anti-tumoral activity of AS101 cancer cells and its mechanism of action are mediated via inhibition of IL-10 and is apoptosis related. AS101 was shown to directly inhibit IL-10 followed by the simultaneous increase of specific cytokines. IL-10 is cardinal cytokine in a wide variety of solid and hematopoietic tumors, and correlates with tumor progression and the metastases. AS101's effect on apoptosis is mediated via inhibition of IL-10 and also by down regulation of the Akt pathway. AS101 was shown to modulate the IL-10 Stat3 loop by down-regulating IL-10 signaling, leading to reduced tyrosine phosphorylation of Stat 3 in IL-10. AS101 induces apoptosis of the malignant cells by up-regulating survivin expression, also in association with the Akt pathway. Akt is known to activate pro-survival genes, among them survivin, which is a main survival factor in many cancer cells. It was shown that treatment of the cells with AS101 results in decreased survivin expression. AS101 might mediate its activity via decrease of Akt activation and survivin protein, thus leading to cellular apoptosis.

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